Preoperative Differentiation of Benign and Malignant Solitary Thyroid Nodules

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 2, NO.3 111

Preoperative differentiation of benign and malignant solitary thyroid nodules

N. ANANTHAKRISHNAN, K. MADHAV RAO, R. NARASIMHAN, K. R. SETHURAMAN, K. S. N. REDDY, A. J. VELIATH

ABSTRACT rately distinguishing benign from malignant nodules, we Between 1977 and 1988 we prospectively studied 503 prospectively studied 503 patients with solitary thyroid patients with solitary thyroid nodules to evaluate the plan nodules over a period of 12 years. of clinical examination, and the role of plain X-rays of the neck, scintiscanning, sonography and fine needle aspira- PATIENTS AND METHODS tion cytology (FNAC) in differentiating benign nodules A detailed clinical profile was available in all the patients, from malignant ones. We found that clinical examination, all of whom had their thyroid nodules excised sub- plain X-rays of the neck and routine thyroid function sequently. These were then subjected to histological studies do not help in such a differentiation. Scintiscanning examination. The clinical features that we considered, on and sonography are not cost beneficial in the majority of patients and help little in identifying patients with malig- the basis of previous reports.l " to favour a diagnosis of nancy. FNAC has limitations which are not well publicized malignancy were: and requires considerable expertise for accurate and 1. male sex confident reporting. Webelieve that in India such investi- 2. age less than 40 years gations are of limited value and should not be routinely 3. recent onset (less than 6 months) with a rapid increase done in the large number of patients with single thyroid in size nodules. 4. presence of pain 5. change in voice or other pressure symptoms INTRODUCTION 6. hard consistency Thyroid nodules are fairly common and are found in 4% 7. evidence of local fixity to 7% of the population in Western countries. 1-4 The 8. palpable regional lymph nodes incidence of malignancy in single thyroid nodules ranges 9. evidence of distant metastases from 5% to 35% (median 20%)5,6 and detailed clinical 10. recurrent laryngeal nerve palsy on laryngoscopy investigation is, therefore, directed primarily at identifying the patients who have solitary, malignant thyroid Investigations included: nodules. . 1. thyroid function tests (117 patients) There are several clinical criteria such as the age and sex 2. plain X-ray of the neck (344 patients) of the patient with the solitary nodule, its duration and 3. radioactive iodine scan (298 patients) rate of growth, its consistency, shape and size and the pre- 4. ultrasonography of the neck (126 patients) sence of pressure symptoms which have been considered 5. fine needle aspiration cytology (FNAC) (150patients) important and have been re-emphasized recently as being The presence of microcalcification on plain X-ray of the useful in distinguishing benign from malignant nodules.? neck, a cold nodule on radioactive scanning, solid or com- Routine investigations may include thyroid function tests, plex lesions on ultrasonography and definitive evidence radionuclide scans, plain X-rays of the neck, contrast on FNAC were all considered to indicate malignancy. radiographic studies, ultrasonography, computerized tomography, magnetic resonance imaging" and FNAC. RESULTS To evaluate which, if any, of these tests helps in accu- Clinical criteria There was no significant difference in the incidence of Jawaharlal Institute of Postgraduate Medical Education and Research, malignancy in males below or above 40 years of age Pondicherry 605006, India (Table I). In females, the incidence of malignancy was N. ANANTHAKRISHNAN, K. MADHAV RAO, K. S. N. REDDY, A. J. VELIATH Department of Surgery higher in those who were over40. There was little differ- R. NARASIMHAN Department of Pathology ence in the overall prevalence of malignancy between the K. R. SETHURAMAN Department of Medicine two sexes. Correspondence to N. ANANTHAKRISHNAN The differences in clinical features between the patients © The National Medical Journal of India, 1989 112 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 2, NO.3 with benign and malignant nodules are shown in Table II. TABLE I. Incidenceof malignancyin variousagegroups Only hoarseness of the voice and a hard consistency were significantly more common in patients with malignant Age group Males Females solitary nodules. We then divided the patients into two (n=126) (n=377) categories: % % a. clinically malignant patients who had hard nodules, Below 20 years 25 (114) 11(4/35) hoarse voice and one other characteristic suggesting 21-40 years 19(13/68) 11 (28/248) malignancy. 41-60 years 17 (8/47) 25 (20/80) b. clinically benign patients in whom these clinical features Above60 years 43 (3/7) 0(0/14) were absent. Overall 20(25/126) 14 (521377) Of the 77 patients in whom malignant nodules were confirmed by operation, only 49 (64%) were in the clini- NB. Figures within parentheses indicate number of patients in each group cally malignant group. The size of the nodules was not related to the risk of malignancy.

Investigations TABLE II. Differences in symptomatology and signs between benignand malignantsolitarynodules On a plain X-ray, fine microcalcification said to be typical of carcinoma of the thyroid was not found in any of the Symptom/sign Benign Malignant p 344 patients. Coarse calcification occurred in two patients (n=426) (n=77) who were subsequently found to have adenomatous goitres. % % Routine thyroid function tests were done in 117 patients: 90% of patients with benign nodules and 97% of Short duration «6 months) 35 29 ns those with malignant nodules were euthyroid. All the 10 Rapid increase in size 4 7 ns patients with benign nodules who had hyperthyroidism Pain 9 16 ns had adenomatous goitres with hyperplasia. Two patients Hoarseness 7 19 0.01 with follicular carcinoma (2.6%) also had hyperthyroidism. Other pressure symptoms 13 17 ns The patients with hypothyroidism had lymphocytic Hard consistency 3 17 0.001 thyroiditis. Local fixity nil nil The results of 1311 scanning are shown in Table III. The Palpable regional lymph nodes 2 5 ns incidence of malignancy in 'cold' nodules was 17% and in Distant metastases 1 patients with 'warm' nodules was 10%. This difference is Recurrent laryngeal nerve palsy 4 ns not significant. All the 'hot' nodules were benign. A patchy uptake was seen in 20 instances--of these 17 were ns not significant benign and 3 were malignant. Ultrasound scanning was done in 126 patients (Table IV). All the wholly cystic nodules were benign. The incidence of malignancy in wholly solid lesions was 22% and TABLE III. Resultsof imagingwith 1311 in those with both solid and cystic elements it was 13%. Solid lesions on ultrasonography, therefore, did not indicate Scan appearance Benign Malignant a higher risk of harbouring malignancy when compared to % % lesions which had a complex ultrasound pattern with both solid and cystic areas. There were 48 nodules which were Warm (90) 90 (81) 10(9) 'solid' on ultrasonography and 'cold' on iodine scanning; Cold (177) 83 (146) 17(31) 12 of these (25%) were malignant, whereas lesions cystic Hot (11) 100(11) nil on ultrasonography but cold on radioisotope scanning Patchy (20) 85 (17) 15(3) were always benign. NB. Figures within parentheses indicate number of patients in each group FNAC was done in 150 patients: 23% of the samples were inadequate for a definite opinion and a further 27% were reported to be follicular neoplasms. A firm opinion was, therefore, possible in only 50% of samples. The false positive rate was low at 5.8%, yielding a specificity rate of TABLE IV. Ultrasonographicappearance 95%. However, a relatively high false negative rate of 38.5% in our hands led to a fall in the sensitivity rate to Ultrasound appearance Benign Malignant 50%. The sensitivity and specificity rates were calculated % % as per standard formulae. Entirely cystic (17) 100(17) nil DISCUSSION Entirely solid (69) 78(54) 22(15) Mixed solid and cystic (40) 88 (35) 13(5) Single nodules in the thyroid are common and some of them are malignant. Patients with solitary thyroid nodules NB. Figures within parentheses indicate number of patients in each group ANANTHAKRISHNAN et al. : BENIGN AND MALIGNANT SOLITARY THYROID NODULES 113

have a higher incidence of malignancy than those with dently between benign and malignant lesions'? and provides multinodular goitres." Clinical and laboratory examina- no additional benefit." Only 25% of scintigraphically tion is directed at identifying benign from malignant cold nodules, which were sonographically solid, were nodules to avoid unnecessary operation. The aim of this malignant; and this agrees with the published data." The study was to determine how successfully this identification current belief is that despite improved sensitivity and might be achieved using conventional tests and whether higher resolution there are no reliable ultrasonographic these influenced the decision to operate. criteria on which a diagnosis of malignancy could be based Certain clinical characteristics have traditionally been and, in fact, in easily palpable nodules which on FNAC said to be more commonly associated with malignancy in proved to be solid; it is a superfluous investigation.s solitary thyroid nodules. Malignancy is said to be commoner FNAC is now being used more frequently but it has in men."? This study, however, showed a higher prevalence several little known disadvantages. In experienced of malignancy in women but the difference between the two hands,I9-26 between 3.3% to 16% of specimens are sexes did not reach statistical significance. Malignancy is reported to be unsatisfactory for characterization and an believed to be more common in patients below the age of additional 8.7% to 33% are reported to be follicular 40 years, especially in those below 20 years of age. 7,9,10We neoplasms which cannot be differentiated into benign and did not find a higher prevalence in younger patients malignant forms.20,27-29 Operative excision is advised to (Table I). In women over 40 years of age malignancy was rule out malignancy." On FNAC, only about 60% of as common as in those below 40 years (43 % ). Of men with single thyroid nodules can be classified as being benign or solitary nodules, all those over 60 years had carcinoma. malignant. Reported accuracy rates, therefore, refer to The clinical differences between patients with benign only this subgroup of patients with single nodules. Within and malignant solitary nodules are listed in Table II. this group there is a further 10% false negative rate and Statistical significance was reached only for hoarseness of about 2.5% false positive rate in most centres." About voice and consistency of nodules. That these two features 15% to 30% of fine needle aspirates are expected to be indicate malignancy has been reported previously." It has. 'suspicious' of malignancy;1I,27,30-36 and surgery will con- also been stated that pain in an enlarging solitary nodule firm only 10% to 50% of these as malignant. Whilst it is may indicate malignancy'! but we did not find pain to be known that occult carcinomas can be missed on FNAC, an important differentiating symptom. We and others'? it is not as well known that a negative finding cannot have not shown any consistent clinical differences between definitely rule out malignancy. 6 Granberg et al. state that patients with benign and malignant solitary nodules. By since diagnostic failure cannot be completely avoided on using the above three features we were unable to distin- FNAC, withholding of surgery may risk the overlooking guish malignant from benign nodules and as many as 28 of of a number of thyroid carcinomas." 77 nodules which were subsequently found to be malignant We conclude, therefore, that clinical differentiation of were clinically classified as benign. benign and malignant nodules cannot be done with certainty As' clinical differentiation cannot be relied upon, it is although certain features may separate a proportion of advisable to use investigative techniques to detect malig- patients with malignant nodules. We found that on the nancy in view of the cost and accompanying morbidity of basis of a clinical examination we could not confidently unnecessary thyroid surgery. A plain X-ray of the neck advise any patient against surgery. Widely used investiga- did not detect the characteristic calcification pattern- tions such as thyroid function tests, radioactive iodine an experience we shared with otherss-=and is thus not cost scanning and sonography may suggest this separation but effective. Conventional thyroid function tests also do not would not justify the cost. Conventional investigations help in identifying benign from malignant nodules. The like scintiscanning and sonography only identify the majority of patients with solitary thyroid nodules are group with a greater chance of malignancy and do not euthyroid,'? and most with hyperthyroidism have benign identify all patients with malignancy. FNAC is useful but nodules. Hypothyroidism, though rare, is never associated has certain inherent limitations besides requiring consider- with carcinoma. able expertise to interpret the aspirated material. 4 Scintiscanning with radioactive iodine is widely used in We believe that in India, with its known resource the investigation of patients with a solitary thyroid nodule. constraints, such investigations should be restricted to a It is, however, an insensitive test for carcinoma'? as the few centres and that too for research purposes. This has majority of 'cold' nodules are benign. The risk of car- recently been corroborated by the experience of richer cinoma in 'cold' nodules is in fact only slightly higher than countries." Therefore, until more accurate methods are that in 'warm' nodules. 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