However, with regard to the growth rate of malignant nodules, results have been non-uniform. One study demonstrated that a large number of papillary microcarcinomas remained relatively stable over a long observation period [ 14 ].
Since thyroid nodules are frequently detected by cervical ultrasound examinations, distinguishing between a benign and a malignant nodule is a relevant clinical challenge.
With respect to current guidelines, it is the sonographic pattern rather than the growth of a nodule that raises suspicions of malignancy [ 15 ]. Depending on the ultrasound pattern, fine-needle aspiration biopsy FNAB is considered the method of choice to detect malignancy.
Consequently, such nodules will be subject to serial follow-up ultrasound examinations. In this retrospective cohort study, we report serial sonographic examinations in 28 malignant and 26 benign thyroid nodules selected from our clinical database and verified by histological analysis. The aim of this study was to test the hypothesis that the growth rates of benign and malignant follicular thyroid nodules, as determined by volumetric ultrasound, do not differ. For this analysis, we also took the intra- and interobserver reproducibility of volumetric ultrasound into account as determined in a subset of 25 separately studied nodules.
All patients gave general permission for the use of their clinical data for scientific purposes and written informed consent for the anonymous publication of data. Demographic, sonographic and pathologic information were obtained from our database. We reviewed patients who were examined between and From our database we could identify 25 patients with thyroid nodules who were assessed with respect to intra- and interobserver variations of sonographic volumetry.
In our database 52 patients were documented who had serial ultrasound examinations of thyroid nodules. At the end of the follow-up period the thyroid nodules represented histologically confirmed differentiated thyroid carcinomas in 26 patients subset B: carcinoma group and histologically confirmed follicular adenomas in 26 patients subset C: adenoma group, respectively. The pathologic examinations were carried out by two board certified pathologists with special expertise of at least 10 years in thyroid tumors.
Only patients with definite histologic diagnoses were includes in our study. Patients with questionable histologic diagnoses were not considered for our evaluation. The ultrasound devices were equipped with high resolution longitudinal probes operating at transmitting frequencies of Sonographic examinations were performed by three board-certified nuclear medicine physicians P1, P2 and P3.
Standardized examination protocols including transverse and longitudinal slice orientations were used for thyroid sonography. All nodules were classified according to the American Thyroid Association classification system [ 15 ] with respect to their risk of malignancy: type 1: benign; type 2: very low risk; type 3: low risk; type 4: intermediate risk and type 5: high risk. The size of the thyroid nodules was measured in three dimensions dx, dy, and dz using the internal calipers of the devices, where dx, dy, and dz represented the diameter in transverse, sagittal, and longitudinal directions, respectively.
These patients were examined using sonography by two physicians P1 and P2 who were blinded to each other at one time point using the two ultrasound devices, D1 or D2. Measurements by P1 using D1 were used as the reference values. Measurements by P1 using D2 were correlated with the reference values to calculate intraobserver variation, and measurements by P2 using D2 were used to calculate interobserver variation.
All patients of these subsets had one initial thyroid ultrasound scan baseline examination at time point t 0 and follow-up examinations at different time points t. Nine of the 26 patients had additional ultrasound examinations between t 0 and T at time point t. The median time between t 0 and T was A total number of 71 ultrasound examinations was carried out in this subset of patients.
All patients had a thyroidectomy and the malignant nature of the thyroid nodule was determined histologically. Twenty-four of the nodules were classified as papillary thyroid carcinomas PTCs and four nodules as follicular thyroid carcinomas FTCs.
Nineteen of the 26 patients had additional ultrasound examinations between t 0 and T at time point t. A total number of 87 ultrasound examinations were carried out in this subset of patients. All patients had a thyroidectomy and the benign nature of the thyroid nodules was confirmed histologically.
Five of the nodules were classified as microfollicular, 12 nodules as macrofollicular and nine nodules as mixed follicular thyroid adenomas. Statistical analyses were performed using Winstat R version Multiple comparisons among observers were performed by repeated measures ANOVA with post hoc Bonferroni corrections and calculations of F values. Differences between two groups were evaluated by using a Wilcoxon rank-sum test.
Differences between frequency parameters were tested using the chi-square test. The mean volume, standard deviation, and minimum and maximum values of all nodules in subsets A, B, and C were 2.
The values of the nodule volumes are shown in Table 2. Two statistical approaches were performed: In the first approach, measurements at time points t 0 and T were taken into account, and in approach two, measurements at all time points were taken into account.
Box plots of the growth rates of malignant subset B and benign subset C thyroid nodules between time points t0 and T approach 1. The whiskers indicate 1. The growth rates of malignant nodules in subset B and benign nodules in subset C were calculated, including measurements at all time points each referred to the first measurement.
Box plots of the growth rates of malignant subset B and benign subset C thyroid nodules among all time points t0 and t approach 2. Both approaches did not reveal different growth rates for malignant and benign nodules.
The values for the growth rates of subsets B and C as well as the subgroups are shown in Tables 3 and 4. In this study, we found no significant differences in the growth rates of malignant and benign thyroid nodules, thus providing a linear model of nodule enlargement. The kinetics of thyroid nodule growth have been subjected to several other investigations. In a previous report by Asanuma et al. In our study the growth rates of only 4 FTCs were analyzed.
In a recent study, Kim et al. In their retrospective study 50 FTCs and follicular adenomas were included. The assumption of a linear progression may not reflect the real growth kinetics of neoplastic tissue. In contrast to this linear model, we found that shorter increments of multiple volume determinations revealed differences in the growth rates between malignant and benign thyroid tumors.
By using multiple volume measurements at shorter increments compared with only two recordings at the initial and final time points, we identified growth rates of malignant nodules that were higher than those of benign tumors.
However, the evidence for this finding in our study is limited since we did not perform ultrasound examinations at shorter increments in all patients.
Others are mixed. In other cases, the nodules can get big enough to cause problems. But even larger thyroid nodules are treatable, sometimes even without surgery.
If concern arises about the possibility of cancer, the doctor may simply recommend monitoring the nodule over time to see if it grows. Ultrasound can help evaluate a thyroid nodule and determine the need for biopsy. A thyroid fine needle aspiration biopsy can collect samples of cells from the nodule, which, under a microscope, can provide your doctor with more information about the behavior of the nodule. Even a benign growth on your thyroid gland can cause symptoms.
If a thyroid nodule is causing voice or swallowing problems, your doctor may recommend treating it with surgery to remove all or part of the thyroid gland. If the doctor recommends removal of your thyroid thyroidectomy , you may not even have to worry about a scar on your neck. Some patients are good candidates for a scarless thyroid procedure , where the surgeon reaches the thyroid through an incision made on the inside of your lower lip.
Growth rate was greater for malignant nodules compared with benign nodules; a growth rate of at least 2 mm per year was present in During follow-up, Nodules that grew more than 2 mm to 4 mm per year had an RR for malignancy of 1. For example, those growing more than 8 mm per year had an RR of 5.
Conversely, nodules that are stable, and especially those decreasing in size, are much more likely to prove benign. Together, these data suggest that thyroid nodule growth and especially rapid nodule growth should be reintroduced as an important variable in the evaluation of follow-up of thyroid nodules. This study brings focus back to the use of growth rate as an independent predictor of malignancy. It is considerably well powered, with analysis of nearly 1, nodules, but its main strength is the comparison of growth rates of malignant nodules with benign nodules, a feature lacking in many long-term growth studies, for obvious reasons.
Careful consideration was given to the possibility of selection bias for this pool of nodules, and the authors, in my mind, have satisfactorily addressed the low likelihood that a bias of this sort could be influencing the data. The results show that nodule growth, defined as greater than 2 mm per year, was indeed an independent predictor of malignancy and that faster growth rates increased the risk.
Furthermore, cancers with higher-risk subtype eg, medullary thyroid cancer, tall cell variant of papillary were even more likely to demonstrate growth over the follow-up period. As we are using more selective criteria to determine which nodules to biopsy, as well as the recent trend toward consideration of observing small known cancers, this study suggests that tracking nodule growth rate is a useful tool in determining appropriate care.
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