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Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi 411-764, Republic of Korea
Address all correspondence and requests for reprints to: Sun Wook Kim, M.D., Department of Endocrinology, Center for Breast Cancer, National Cancer Center, Madu-1-dong 809, Ilsan, Goyang, Gyoenggi 411-764, Republic of Korea. E-mail: swkim{at}ncc.re.kr.
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Abstract |
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Thyroid incidentalomas are defined as newly identified thyroid lesions encountered during imaging study, e.g. ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), for nonthyroid diseases (4). According to an autopsy series in individuals without a previous history of thyroid diseases, the prevalence of thyroid nodules was up to 51% (5). High resolution US examinations report a prevalence of thyroid nodules ranging from 19–46% in the general population; however, the associated risk of cancer is very low and ranges from 1.5–10% in these thyroid incidentalomas. Moreover, none of these previously mentioned (US, CT, and MRI) studies are specific for thyroid malignancy (6, 7, 8).
Cohen et al. (9) reported in a retrospective review of FDG-PET studies that thyroid FDG-PET incidentaloma was found in 2.3% of a group of patients who underwent FDG-PET for the metastatic evaluation of cancer, and 47% of those incidentalomas, with an available pathological diagnosis, turned out to be malignant. Van den Bruel et al. (10) also reported a high risk of cancer in a series of thyroid FDG-PET incidentalomas. As FDG-PET is becoming a much more common imaging modality, the incidence of thyroid FDG-PET incidentaloma is also increasing and is becoming a problem to both patients and the doctors who deal with this problem in terms of the extent of work-up required because of the high likelihood of cancer according to previous reports (9, 10, 11, 12).
The prevalence of thyroid FDG-PET incidentaloma in the general population has not been reported, because of the high cost of FDG-PET examination. Although there is much debate on the cost-effectiveness of FDG-PET for cancer screening, we have used FDG-PET as part of a voluntary cancer-screening program in healthy subjects without a previous history of malignancy (2, 3).
In this study we performed a retrospective review of our institutional experience of thyroid FDG-PET incidentaloma in two groups of subjects (i.e. in a patient group who underwent FDG-PET for the evaluation of metastasis of cancer and in healthy subjects without previous history of malignancy for voluntary cancer screening). The prevalence of thyroid FDG-PET incidentaloma was compared in these two groups. The risk of malignancy of thyroid FDG-PET incidentaloma and its association with the standard uptake value (SUV) of FDG-PET was evaluated.
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Subjects and Methods |
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The data from all FDG-PET studies conducted from June 20, 2001, to December 31, 2002, were analyzed retrospectively. At our institution we perform FDG-PET for two different purposes: as a metastasis evaluation in cancer patients and as a cancer-screening program in presumptively healthy subjects who have no previous history of malignancy and volunteer for this program. Our institution has cancer-screening programs organized by the Department of Cancer Prevention and Early Detection. The screening program is divided into basic and extended programs. The basic program is focused on screening six of the most common cancers in Korea (stomach, lung, liver, colon, breast, and cervical cancer). FDG-PET examination is part of an extended program for additional coverage of less frequent cancers, such as biliary cancer, pancreatic cancer, and other less frequent solid organ cancers. Of course, it is not customary outside Korea or Japan, and it is not generally suited for the usual cancer-screening program considering the substantial cost. For those who wanted to undergo a cancer-screening program, we did not intervene in their decision of choosing the basic or extended program, but explained benefits, limitations, and cost for both the basic and extended programs. Therefore, we believe that the risk factors of subjects who undergo a basic or extended program are not different. On the basis of other laboratory results and incidence of cancer detected by these cancer-screening programs at our institution, the risk of cancer in subjects who underwent either the basic or extended cancer-screening program is not significantly different from that of general population, but the socioeconomic status of the subjects who undergo a cancer-screening program is higher, because they pay for it themselves. A total of 1345 subjects underwent the FDG-PET study during this period. Fifteen patients who underwent FDG-PET for the evaluation of a thyroid-related malignancy were excluded from the analysis. Thus, 1330 subjects were included in this analysis. Among them, 1014 patients underwent the FDG-PET examination for metastasis evaluation of cancer, and 331 underwent FDG-PET for part of above-mentioned cancer-screening program in presumptively healthy subjects.
PET method
PET scans were obtained on a dedicated whole body PET scanner (ADVANCE, GE Medical Systems, Milwaukee, WI). All patients were fasted, except water, for at least 8 h before their PET study. Image acquisition for the whole body scan started about 60 min after the iv administration of 370–555 MBq (10–15 mCi) FDG. Five bed positions were examined with 5 min for each step for the whole body emission scans, and the postinjection transmission scans were followed with 3 min/step. Emission tomographic images were reconstructed using the iterative ordered subsets expectation maximization algorithm. The segmented attenuation correction was performed using the transmission images.
Thyroid incidentaloma was defined as thyroid uptake identified on FDG-PET study incidentally, and it was divided into focal and diffuse types according to the thyroid uptake pattern of FDG. Focal uptake was defined as FDG uptake in less than one lobe, and diffuse uptake was defined as FDG uptake in the whole thyroid gland.
The maximum SUVs (SUVmax) of the thyroid lesions were recorded, and the average values, which included pixels greater than 0.75 threshold of SUVmax (SUV0.75max), were calculated to eliminate the possibility of a noise effect when only SUVmax were considered (13). Each region of interest, for calculating SUV0.75max, was drawn over the tumors on the transverse slice containing SUVmax. FDG-PET examinations were reviewed by two nuclear medicine physicians to define the pattern of uptake and the SUVs of the thyroid incidentaloma.
Histology diagnosis of focal thyroid FDG-PET incidentaloma
In 15 of 21 focal thyroid FDG-PET incidentalomas, we obtained histology diagnosis by either US-guided core needle biopsy (n = 7) or surgical resection of tumor (n = 8). In US-guided core needle biopsy, we used an Acecut (TSK Laboratory, Tochigi, Japan) biopsy gun with a modified method to acquire a histology specimen of the thyroid nodule. In the conventional manner, the Acecut biopsy gun has double action in a stepwise mode, with firing of the core needle first and firing of the sheath needle later. The two firings occur one after the other, just after the firing button is pushed by the operator. In the modified method, we first fired the core needle before inserting the gun into the patient’s body. We inserted the gun where the first core needle was fired, and penetrated the target nodule with the core needle under US guidance. This method has the advantage that there is no more advance of the needle beyond the tip of the core needle, thus avoiding the risk of firing in an unexpected direction.
Statistics
2 analysis was carried out using SPSS (version 9.0, SPSS, Inc., Chicago, IL) to determine the prevalence difference of thyroid incidentaloma according to the purpose of the FDG-PET study (between those with underlying malignancy and those who underwent FDG-PET examination for routine health screening). Two-tailed t testing was used to compare SUVmax and SUV0.75max for malignant and benign lesions of the focal thyroid FDG-PET incidentaloma. Both tests were considered significant at an overall P < 0.05.
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Results |
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Data were analyzed according to the purpose of the FDG-PET scan. Nineteen (13 focal and six diffuse) of the 999 patients (1.9%) who underwent FDG-PET for the metastasis evaluation of malignancy were identified as having thyroid incidentaloma, and 10 (eight focal and two diffuse) of the 331 subjects (3.0%) in the cancer-screening program were identified with thyroid incidentaloma. There was no statistically significant difference in the prevalence between these two groups (19 of 999 vs. 10 of 331; P = 0.27). When we analyzed the difference only for focal incidentaloma, there was also no statistical difference in the prevalence between the two groups (13 of 999 vs. 8 of 331; P = 0.20).
Histological diagnosis was available in 15 of 21 focal thyroid FDG-PET incidentalomas (eight confirmed by surgery and seven confirmed by US-guided core needle biopsy). Histological diagnosis and FDG-PET study data in this group of patients are listed in Table 1
. Among six patients whose histology diagnosis was unavailable, two patients received no further work-up due to a poor general condition, three patients refused further work-up, and one had an inadequate pathological report. In four of the 15 patients (26.7%) with focal thyroid FDG-PET incidentaloma, the tumor was found to be malignant, and all were papillary thyroid carcinoma. Another three focal incidentalomas revealed follicular adenoma confirmed by thyroidectomy, one follicular neoplasm was diagnosed by US-guided core needle biopsy, and the remaining seven were adenomatous goiters.
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.) There was one overlapped case in SUV in which one benign follicular adenoma confirmed by thyroidectomy showed an SUVmax of 16.0 (SUV0.75max = 12.4), which is above the lower limit of thyroid cancer patients (SUVmax= 11.8; SUV0.75max= 8.7). Otherwise, all malignant and benign lesions were clearly distinguished by the SUVs (Table 1
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and 3.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Yet there has been no report about the prevalence of thyroid FDG-PET incidentaloma in the general population. Of course, healthy subjects who underwent FDG-PET for cancer screening in this study may not represent the general population. However, because of the high cost of FDG-PET and the low incidence of thyroid FDG-PET incidentaloma, we cannot use FDG-PET to evaluate the prevalence and risk of cancer of thyroid FDG-PET incidentaloma in the real general population. Therefore, considering the lack of a difference among blood thyroid function tests, other laboratory values, and incidence of cancer between subjects who underwent a cancer-screening program at our institution and the known values of the general population, we cautiously presumed that those who underwent FDG-PET for cancer screening might closely represent the general population in terms of the prevalence of thyroid FDG-PET incidentaloma, and this value was 3.0%.
The prevalence of thyroid FDG-PET incidentaloma in the group for metastasis work-up was no higher than that in the cancer-screening group. On the contrary, it was a little lower, although this was not statistically significant (1.9% vs. 3.0%; P = 0.27). We believe that this is due to the ages of the two groups (i.e. there was a larger proportion of young age subjects in the metastasis work-up group (<35 yr, 7.8% in metastasis work up group; 4.2% in the cancer-screening group; it is known that thyroid nodule and thyroid cancer increases with age).
Ramos et al. (16) reported that focal thyroid FDG-PET uptake might represent second primary tumor . All cancers identified as thyroid FDG-PET incidentalomas were papillary thyroid carcinoma in this study, and no metastatic thyroid cancer was identified in either focal or diffuse incidentaloma. Therefore, it is recommended that focal thyroid FDG-PET incidentaloma in patients with underlying malignancy should not be considered as metastatic cancer without tissue confirmation, but has a high likelihood of primary thyroid carcinoma, and such individuals should be diagnosed thoroughly if the thyroid pathology changes the patient’s treatment plan or the disease course.
Most centers use fine needle aspiration cytology or biopsy with or without US guidance as the initial diagnostic method for thyroid nodule because of its high diagnostic accuracy (15, 17, 18). In this study we were able to acquire histological diagnoses for most of the focal thyroid incidentalomas (15 of 21, 71.4%) by either surgery or US-guided core needle biopsy. Therefore, selection bias for histological diagnosis, which may be present in Cohen’s study, in which only 15 (21%) of 71 focal thyroid FDG-PET incidentaloma patients underwent thyroid biopsy (9), was reduced. Four of 15 (26.7%) thyroid FDG-PET incidentalomas were papillary thyroid carcinomas, and no metastatic thyroid cancer was identified. Although the risk of cancer of the thyroid FDG-PET incidentaloma is lower than that (47%) reported by Cohen et al. (9), this value is much higher than that of other thyroid incidentalomas identified by US, CT, or other diagnostic modalities (8). This result indicates a high risk of malignancy in the focal thyroid FDG-PET incidentaloma and is in agreement with other reports of thyroid FDG-PET incidentalomas (9, 10, 11).
We did not evaluate the histology of diffuse thyroid FDG-PET incidentaloma because previous reports indicate that the majority represent chronic thyroiditis or Graves’ disease and generally do not need histological diagnosis, except in a small number of conditions (12, 19). In agreement with Yasuda et al. (19), who reported the benign nature (chronic thyroiditis) of thyroid disease in 36 diffuse uptakes by FDG-PET, we found no evidence of malignant diseases in 8 cases of diffuse uptake in our series as mentioned in Results. Thus, we think that the risks of cancer for focal and diffuse thyroid incidentaloma by FDG-PET are quite different.
Several studies have been performed to accurately identify malignant thyroid nodule from benign nodule using the SUV of FDG-PET (20, 21). In this study a high SUVmax or SUV0.75max implied a high likelihood of cancer (P < 0.05), especially when the SUVmax is above about 9 (SUVmax of malignant nodule; 95% CI, 9.0–24.1). Although there was a statistically significant difference between malignant and benign lesions, there was one overlapped case. One benign follicular adenoma confirmed by thyroidectomy had an SUVmax of 16.0 and an SUV0.75max of 12.4, whereas the minimum SUVmax and minimum SUV0.75max of thyroid cancer were 11.8 and 8.7, respectively. Except for this case, all thyroid cancers had higher SUVs than the benign lesions. Thus, the possibility of differentiating malignant from benign lesions with SUVs of FDG-PET, especially as for follicular neoplasm by fine needle aspiration or thyroid biopsy, could be considered. However, the findings of the present study do not provide answers to this question because of the small number of follicular neoplasm cases (four cases). Therefore, we are now investigating the efficacy of FDG-PET in differentiating malignant from benign follicular neoplasm when used in combination with FNA cytology or biopsy.
In conclusion, 29 (2.2%) of 1330 subjects who underwent FDG-PET scanning showed thyroid incidentaloma (21 focal and eight diffuse), and no statistically significant difference was observed in the prevalence of thyroid FDG-PET incidentaloma according to the purpose of the FDG-PET examination (metastasis evaluation vs. cancer screening in healthy subjects without a previous history of malignancy). Focal thyroid FDG-PET incidentaloma is associated with a high risk of malignancy (26.7%), whereas diffuse incidentaloma is not. The SUVmax or SUV0.75max of thyroid cancer is significantly higher than that of benign lesions, and the SUVmax and SUV0.75max could serve as indexes of thyroid malignancies, but more data are required. Therefore, we recommend that a pathological diagnosis, by either histology or cytology examination, of focal thyroid FDG-PET incidentaloma with high SUV is necessary if the nature of the thyroid disease changes a patient’s treatment plan or disease course.
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Footnotes |
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Received March 17, 2003.
Accepted June 9, 2003.
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