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 » Introduction
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 1  |  Page : 186-189
 

Positron emission tomography thyroid incidentaloma: Is it different in Indian subcontinent?


1 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication28-Apr-2016

Correspondence Address:
A K D’cruz
Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.180860

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 » Abstract 

Background: Positron emission tomography (PET) forms an integral part in work-up and follow-up of various malignancies. With the increased use of PET in oncology, finding of an incidental focal thyroid uptake (incidentaloma) is not unusual and presents a diagnostic challenge. Aim: The aim of the following study is to evaluate the frequency and radio-pathologic correlation of focal 18-fluoro deoxyglucose uptake (FDG) on PET within the thyroid from a large series. Materials and Methods: Retrospective review of 37,000 consecutive patients who underwent FDG-PET at tertiary cancer center in India. Radiological, pathological, PET scan and follow-up details were evaluated. Statistical analyzes were carried out using Mann Whitney test and Pearson correlation. Results: Abnormal thyroid uptake was seen in 78 (0.2%) patients. Nearly 61 (0.16%) scans had focal and 17 (0.04%) had diffuse FDG uptake. A total of 57 patients with focal uptake were available for further evaluation. No further evaluation was done in 24 (42.1%) patients who had advanced index malignancy. Of the remaining 33 patients 26 were benign and seven were a cause for concern (four primary thyroid cancers, one follicular neoplasm with hurthle cell change and two metastatic cancers). There was no significant correlation in Standardized uptake value (SUV) max of benign and malignant lesion (P = 0.5 on Mann Whitney) or size (r = 0.087 Pearson correlation co-efficient P= 0.667). Conclusion: Incidence of PET incidentaloma is low in this large cohort of Indian patients. Nearly 27% of focal incidentaloma were malignant. There was no correlation between the SUVmax, size and malignancy.


Keywords: Fine- needle aspiration cytology, positron emission tomographyPET CTcomputer tomography, thyroid carcinoma, thyroid incidentaloma, ultrasound of neck


How to cite this article:
Vaish R, Venkatesh R, Chaukar D A, Deshmukh A D, Purandare N C, D’cruz A K. Positron emission tomography thyroid incidentaloma: Is it different in Indian subcontinent?. Indian J Cancer 2016;53:186-9

How to cite this URL:
Vaish R, Venkatesh R, Chaukar D A, Deshmukh A D, Purandare N C, D’cruz A K. Positron emission tomography thyroid incidentaloma: Is it different in Indian subcontinent?. Indian J Cancer [serial online] 2016 [cited 2019 Sep 17];53:186-9. Available from: http://www.indianjcancer.com/text.asp?2016/53/1/186/180860



 » Introduction Top


Incidentally detected thyroid lesion by a diagnostic modality used for a non-thyroidal disorder is termed as incidentaloma. The incidence of detecting incidentaloma varies with the investigational modality used. It is highest following ultrasound (USG) where incidentaloma could be detected in up to 50% of patients.[1],[2],[3] Positron emission tomography (PET) associated incidentalomas are fortunately, not as common and have reported incidence in literature varying from 1.0 to 2.2%.[4],[5],[6] These however are considered to be the most ominous of all incidentalomas with the incidence of malignancy as high as 50%.[4],[5],[7],[8] This poses a management challenge on the clinician as patients are already under treatment/evaluation for another cancer. Such is the dilemma in the management of these lesions that it has been described as PAIN (PET Associated Incidental Neoplasm of thyroid) in literature.[9]

Although there have been many publications in the literature on PET incidentalomas the majority are from the western world and with limited numbers. This study is one of the largest (37,000 consecutive cases) from the Indian subcontinent. This is all the more relevant given the huge difference in the incidence of thyroid cancer in the western world compared with south East Asian subcontinent. In the year 2010, incidence of thyroid malignancy in USA was 38,215 cases while in India was 13,540[10] which is significantly lower given the difference in population in the two countries. With this background, there is clearly a need to analyze the incidence of incidentaloma in the Indian subcontinent.


 » Materials and Methods Top


Patient selection

Records of all patients who underwent PET-computed tomography (CT) studies at tertiary cancer center between January 2005 to December 2010 were reviewed. PET CT scans were obtained using bismuth germanium oxide BGO plus, full ring PET/CT (GE Discovery ST). All patients fasted, except for water, for 6h before their PET study. Image acquisition for the whole-body scan started approximately 60 min after the intravenous administration of 370 MBq 18 fluoro deoxy glucose (FDG). Five to six bed positions were examined. Attenuation correction was performed with the CT scan.

A total of 37,000 PET scans were performed during the study period. All patients had PET examinations performed as part of the initial assessment of index cancer or as a follow-up surveillance scan. A thyroid incidentaloma was defined as uptake within the thyroid on PET-CT examination in a patient without prior history of thyroid disease. The PET examinations of these patients were reviewed to describe the patterns and the intensity of FDG uptake. Depending upon the uptake pattern of FDG it was divided into focal and diffuse type. 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 images were interpreted by an experienced nuclear physician. FDG uptake was quantified in the regions of interest on the visible lesions with increased tracer uptake and maximum SUV were calculated.[11]

Records of the subset of patients with thyroid incidentalomas (n = 78) were reviewed for age, sex, cytology, histopathology (lobectomy or thyroidectomy specimens) and ultrasonography. No further work-up was done in patients with advanced index cancer. The remaining underwent further characterization of the nodule with USG, fine-needle aspiration cytology (FNAC) or both. The USG features used for characterization are described elsewhere in the article.[12]

A total of 20 patients underwent USG guided fine-needle aspiration cytology of the thyroid incidentalomas, six patients underwent only fine-needle aspiration cytology and seven underwent only USG. The patients diagnosed to have incidentaloma underwent FNAC using standard technique described elsewhere.[13] The grading of the cytology specimen was done using Bethesda system of classification.[14]

Statistics

Data analysis was carried out using SPSS (version 16.0, SPSS, Inc., Chicago, IL). The difference in SUVmax between benign and malignant groups was analyzed by a Mann Whitney test. Pearson correlation test was performed to find a correlation between SUVmax and maximal diameter of nodule proven as carcinoma on cytologic or histologic examination. All tests were considered to be significant at P < 0.05.


 » Results Top


Thirty seven thousand patients with non-thyroid malignancy underwent PET CT scan in tertiary cancer center. Seventy eight (0.2%) subjects were found to have focal or diffuse FDG uptake. Sixty one (0.16%) showed the focal uptake and 17 (0.04%) were with diffuse uptake. In the 61 subjects with the focal uptake 13 (21.3%) were males and 48 (78.7%) were female (mean age 54.52 ± 11.86, range 11-75). In the 17 subjects with the diffuse uptake there were 4 (23.5%) males and 13 (76.5%) females (mean age 54.82 ± 9.72, range 35-71) [Figure 1].
Figure 1: Focal incidentaloma: work-up #: 4 patients lost to follow-up. *: Either had advanced index cancer, distant metastasis or no nodules on serial scans. **: In 7 patients no fine-needle aspiration cytology was performed as these cases either had no nodule or <0.5 cm with no suspicious feature on the ultrasonography

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Patients with focal thyroid FDG Uptake (n = 61) were evaluated depending on the size of the nodule, age and general condition, prognosis of the index malignancy. Only 57 focal incidentalomas were available for further evaluation and four cases were lost to follow-up. No evaluation was done in 24 (42.1%) patients as six of these patients had distant metastasis, 13 patients were on the palliative treatment due to loco regionally advanced index malignancy and five patients who were treated with systemic chemotherapy or radiotherapy for index malignancy did not have the nodule on the serial scans.

Of the remaining 20 patients underwent USG guided FNAC, six patients underwent only FNAC and seven patient underwent only USG. No, FNAC was performed in seven cases because four did not have a well-defined nodule on Ultrasonography and three had nodules <0.5 cm with no features suspicious of malignancy.

Cytologic diagnosis was available in 26 of 57 focal thyroid FDG-PET incidentalomas. The tumor was found to be malignant in 7 of the 26 patients with focal thyroid incidentaloma with available cytologic findings. Five (19.23%) were primary thyroid malignancy three papillary carcinoma, one follicular carcinoma and one follicular neoplasm with hurthle cell change. 2 (7.69%) patients had contiguous spread from the carcinoma esophagus. The mean diameter was 2.09 cm ± 1.01 (range 0.9-3.3) cm. Among the four thyroid cancer and one follicular neoplasm the diameters of one nodule was <1 cm and those of four nodules were between 1 and 4 cm. Two patients with cytologic diagnosis of papillary carcinoma and one patient with follicular neoplasm underwent total thyroidectomy. Post-operative pathologic examination confirmed the diagnosis of carcinoma. One patient with the papillary carcinoma was 70-year-old female patient with poor general condition and lung metastasis from index malignancy and hence was not operated. One patient with follicular neoplasm had advanced index cancer and was on the palliative treatment and hence no surgery was performed for the thyroid neoplasm. Two patients with metastatic disease were carcinoma esophagus with very advanced disease and under palliative treatment.

There was no significant difference in the SUVmax of the benign and malignant nodule (P = 0.5 on Mann Whitney test). There was no significant correlation between the size and SUVmax of the nodule proven for malignancy pathologically (r = 0.087 Pearson correlation co-efficient P = 0.667). All the histopathologically proven malignant nodules showed focal FDG uptake qualitatively.


 » Discussion Top


Thyroid incidentalomas are a management challenge and much has been written in literature in the past decade. In our study of 37,000 cases the incidence was 0.2% (n = 78) which is much lower than that reported in the literature.[15]

The incidence of the focal incidentaloma which is the cause of concern was 0.16% (n = 61) in our study. This is also much lower than reported incidence of focal incidentaloma in literature which ranges from 1.0% to 2.2% respectively.[4],[5],[6]

This difference in incidence should be considered significant given the large number of patients who underwent PET scanning in our study. The probable reason for this could be the lower incidence of thyroid malignancy in Asian subcontinent (incidence of 7.2 in females and 2.2 in males/100,000 person years) as compared to western population (incidence of 10.0 in females and 3.5 in males/100,000 person years).[16]

However of patients with focal incidentaloma the incidence of malignancy was similar to that reported in the literature. Five (19.23%) out of 26 were primary thyroid malignancy and two (7.69%) were metastatic involvement of the thyroid from the carcinoma esophagus in our study. Studies have shown the incidence of malignancy ranging from 14% to 50% respectively.[4],[5],[7],[8]

Of the five primary thyroid malignancy in our study three were papillary carcinoma, one follicular carcinoma and one follicular neoplasm with hurthle cell change. The most common primary thyroid malignancy was papillary carcinoma. Shie et al. in their review article also found the most prevalent thyroid malignancy in these nodules to be papillary carcinoma.[4] This is not surprising as papillary thyroid cancer is the most common malignancy involving the thyroid gland.

It is important to note that both papillary and follicular lesions show up as focal FDG avid nodules as in our study and distinguishing the two can only be corroborated on cytology. Kresnik et al. also described similar findings in their publication.[17]

Although our series had two cases of focal uptake being malignant from a non-thyroid cancer both were the result of contiguous involvement from adjoining esophageal cancer. Our series did not reveal any case of metastatic index cancer to the thyroid which has been reported in the literature to occur in about 1.25%[18] cases in unselected autopsy study. The common sites of metastatic lesions to the thyroid are kidney, breast and lung. Kim et al. has reported the metastatic involvement of the thyroid from the esophagus and breast malignancy.[8]

FDG uptake can be diffuse or focal. Diffuse uptake on PET CT is usually benign inflammatory condition like thyroiditis and therefore further evaluation is not warranted Focal uptake is associated with malignancy and all malignant nodules in our series showed focal FDG uptake qualitatively. This is in accordance with what has been reported in the literature.[19] American Thyroid Association guidelines recommend a FNAC evaluation in all thyroid nodules over a centimeter.[20] Given the increased incidence of malignancy in PET incidentalomas (up to 50%) sub centimeter nodules should also be needled.[4],[5],[7],[8] Further evaluation of these lesions should be done with USG. Certain features such as micro calcification, irregular margins and incomplete halo increase the probability of malignancy.[12],[21]

The exception to this rule is if the patient's general condition is poor or the index cancer too advanced and out of the realm of curative treatment. No, FNAC was performed in our study in three cases when the nodule was less than a centimeter (<.5 cm, no features of malignancy on sonography and in the opinion of the clinician treating the index cancer took precedence over establishing a diagnosis of thyroid malignancy). This is a fair approach given the majority of cancers will be differentiated papillary tumors with a slow rate of growth of 1-2 mm/year.

PET scans are usually done in patients with locally advanced cancers or as a surveillance follow-up. These groups of patients usually have widespread distant metastasis or compromised general condition with an overall poor survival. Further evaluation of thyroid incidentalomas in these patients is not warranted. In our series, a similar approach was adopted in 24 of 57 patients. This has also being described by others that further evaluation of PET incidentalomas is not worth performing in advanced disease or poor general condition.[22]

SUV values are non-contributory in distinguishing between benign and malignant nodules. This was a finding in our study and also described in the literature. Partial volume effect has been reported in the literature that small lesions have low SUVmax.[23] However in our study, out of five primary thyroid malignancies 3 were <2.5 cm but none <0.9 cm. The probable reason could be that PET is a biological imaging which is based on the glucose metabolism and cannot categorically distinguish between the malignancy, inflammation and the two co-existing together.

Usually larger nodules are associated with an increased incidence of malignancy. There was also no correlation between the SUV values and the size of the nodule in our study. Studies in the literature are contradictory regarding this issue. Some studies found a correlation while some did not find any.[15] The probable reason could be that the SUVmax apart from size would also depend on the glucose transporter 1 (GLUT1) expression in the lesion an important aspect that influences isotope uptake. The expression of GLUT1 is variable in thyroid cancer and varies with the differentiation.[24] The majority of thyroid cancers are known to be well-differentiated which therefore accounts for this phenomenon.

Some surgeons justify excision of all PET incidentalomas given the increased incidence of malignancy. However, this approach is questionable given the high incidence of the thyroid nodules in the general population (4-8%) which may go as high as 50-60% on an autopsy performed for other causes.[25],[26] Most of these have indolent cancers and do not manifest in the lifetime of a person. Ito et al. conducted an observational study [27] in which 70% malignant nodules (< cm) did not show any increase in size over the period of 4 years and only 10.2% of them enlarged over a centimeter. Disease recurrence rate was 5% at 8 years after surgery and there were no disease-specific deaths. This clearly emphasizes the fact that majority of thyroid cancers are an indolent disease, not requiring surgery and the majority of these can safely be left alone. There is also the added concern that the index cancer treatment takes priority over an incidentally detected thyroid malignancy. Treatment of thyroidal lesions should therefore be decided in the light of the clinical assessment and after gauging the prognosis of the disease the PET was performed for as these incidentaloma will rarely be fatal.


 » Conclusion Top


The incidence of the abnormal FDG uptake on PET scan performed for non-thyroid malignancy is low in the Indian setting and the majority of these are benign even with focal FDG uptake. The SUVmax could not differentiate between the benign and the malignant nodules. Index cancer status and general condition should be factored into the treatment algorithm in the management of these patients.


 » Acknowledgment Top


Arti Kanujia for helping with the statistics.

 
 » References Top

1.
Tomimori E, Pedrinola F, Cavaliere H, Knobel M, Medeiros-Neto G. Prevalence of incidental thyroid disease in a relatively low iodine intake area. Thyroid 1995;5:273-6.  Back to cited text no. 1
    
2.
Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009;39:699-706.  Back to cited text no. 2
    
3.
Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med 1994;154:1838-40.  Back to cited text no. 3
    
4.
Shie P, Cardarelli R, Sprawls K, Fulda KG, Taur A. Systematic review: Prevalence of malignant incidental thyroid nodules identified on fluorine-18 fluorodeoxyglucose positron emission tomography. Nucl Med Commun 2009;30:742-8.  Back to cited text no. 4
    
5.
Chen YK, Ding HJ, Chen KT, Chen YL, Liao AC, Shen YY, et al. Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for cancer screening in healthy subjects. Anticancer Res 2005;25:1421-6.  Back to cited text no. 5
    
6.
Kang KW, Kim SK, Kang HS, Lee ES, Sim JS, Lee IG, et al. Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subjects. J Clin Endocrinol Metab 2003;88:4100-4.  Back to cited text no. 6
    
7.
Cohen MS, Arslan N, Dehdashti F, Doherty GM, Lairmore TC, Brunt LM, et al. Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose-positron emission tomography. Surgery 2001;130:941-6.  Back to cited text no. 7
    
8.
Kim TY, Kim WB, Ryu JS, Gong G, Hong SJ, Shong YK. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: High prevalence of malignancy in thyroid PET incidentaloma. Laryngoscope 2005;115:1074-8.  Back to cited text no. 8
    
9.
Katz SC, Shaha A. PET-associated incidental neoplasms of the thyroid. J Am Coll Surg 2008;207:259-64.  Back to cited text no. 9
    
10.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v 2.0. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://www.globocan.iarc.[Last accessed on 2012 Dec 2].  Back to cited text no. 10
    
11.
Sugawara Y, Zasadny KR, Neuhoff AW, Wahl RL. Reevaluation of the standardized uptake value for FDG: Variations with body weight and methods for correction. Radiology 1999;213:521-5.  Back to cited text no. 11
    
12.
Kim EK, Park CS, Chung WY, Oh KK, Kim DI, Lee JT, et al. New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. AJR Am J Roentgenol 2002;178:687-91.  Back to cited text no. 12
    
13.
Pitman MB, Abele J, Ali SZ, Duick D, Elsheikh TM, Jeffrey RB, et al. Techniques for thyroid FNA: A synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:407-24.  Back to cited text no. 13
    
14.
Cibas ES, Ali SZ, NCI Thyroid FNA State of the Science Conference. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009;132:658-65.  Back to cited text no. 14
    
15.
Pampaloni MH, Win AZ. Prevalence and characteristics of incidentalomas discovered by whole body FDG PETCT. Int J Mol Imaging 2012;2012:476763.  Back to cited text no. 15
    
16.
Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, et al. International patterns and trends in thyroid cancer incidence, 1973-2002. Cancer Causes Control 2009;20:525-31.  Back to cited text no. 16
    
17.
Kresnik E, Gallowitsch HJ, Mikosch P, Stettner H, Igerc I, Gomez I, et al. Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area. Surgery 2003;133:294-9.  Back to cited text no. 17
    
18.
Berge T, Lundberg S. Cancer in Malmö 1958-1969. An autopsy study. Acta Pathol Microbiol Scand Suppl 1977;260:1-235.  Back to cited text no. 18
[PUBMED]    
19.
Are C, Hsu JF, Schoder H, Shah JP, Larson SM, Shaha AR. FDG-PET detected thyroid incidentalomas: Need for further investigation? Ann Surg Oncol 2007;14:239-47.  Back to cited text no. 19
    
20.
American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.  Back to cited text no. 20
    
21.
Tomimori EK, Camargo RY, Bisi H, Medeiros-Neto G. Combined ultrasonographic and cytological studies in the diagnosis of thyroid nodules. Biochimie 1999;81:447-52.  Back to cited text no. 21
    
22.
Iyer NG, Shaha AR, Silver CE, Devaney KO, Rinaldo A, Pellitteri PK, et al. Thyroid incidentalomas: To treat or not to treat. Eur Arch Otorhinolaryngol 2010;267:1019-26.  Back to cited text no. 22
    
23.
Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48:932-45.  Back to cited text no. 23
    
24.
Schönberger J, Rüschoff J, Grimm D, Marienhagen J, Rümmele P, Meyringer R, et al. Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: An immunohistochemical study. Thyroid 2002;12:747-54.  Back to cited text no. 24
    
25.
Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955;15:1270-80.  Back to cited text no. 25
[PUBMED]    
26.
Furmanchuk AW, Roussak N, Ruchti C. Occult thyroid carcinomas in the region of Minsk, Belarus. An autopsy study of 215 patients. Histopathology 1993;23:319-25.  Back to cited text no. 26
    
27.
Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003;13:381-7.  Back to cited text no. 27
    


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