Special Article - Thyroid Medicine
Annals Thyroid Res. 2017; 3(1): 89-91.
False-Positive Iodine Uptake in a Patient with Differentiated Thyroid Cancer: A Rare Case of Uptaking Bronchoceles
Mele C1,2, Samà MT¹, Bisoffi AA¹, Orsini F³, Mauri MG¹, Marzullo P1,2, Aimaretti G¹ and Pagano L¹*
¹Department of Translational Medicine, University of Piemonte Orientale, Italy
²Division of General Medicine, Istituto Auxologico Italiano, Italy
³Department of Nuclear Medicine, University Hospital “Maggiore della Carità”, Italy
*Corresponding author: Pagano L, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
Received: December 27, 2016; Accepted: January 23, 2017; Published: January 26, 2017
Introduction: Radioiodine is used for diagnosis and treatment of differentiated thyroid cancer. Thyroid cells most effectively express the Sodium- Iodide Symporter (NIS), which enables iodine uptake; however, NIS is also expressed in inflamed tissues.
Methods: This is a report on a 58 year old woman with a papillary thyroid cancer and false-positive pulmonary radioiodine (131I) uptakes at the Whole Body Scan (WBS).
Case Report: Two radioiodine treatments during withdrawal of levothyroxine were performed, with evidence of pulmonary 131I uptake. A chest Computed Tomography (CT) revealed the presence of multiple acinar opacities associated with thickening of the peripheral bronchi in both lungs, showing an uptake (SUV 8.17) at the subsequent 18F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT). Broncho-alveolar lavage and cytological examination were compatible with inflammation, confirming the suspicion of bronchocele.
Conclusion: Several cases of unexpected 131I uptakes have been reported so far. Therefore, WBS uptake should be correlated with clinical, biochemical data and radiological imaging in order to reduce the false-positive incidence and to avoid unnecessary treatments.
Keywords: Thyroid cancer; Bronchocele; False positive; Whole body scan; Radioiodine
Differentiated Thyroid Cancer (DTC) is usually treated with surgery, Radioiodine Ablation Therapy (RAI) and Levotiroxine Therapy (L-T4). In particular, radioiodine has been used for more than five decades for the diagnosis and treatment of patients with DTC. The efficacy of the RAI is due to the ability of the thyroid cells to concentrate iodine, owing to the expression of the Sodium-Iodide Symporter (NIS) on the thyroid cell membrane, which mediates trapping, organification, and storage of radioiodine (131I) especially in functioning thyroid tissues [1,2].
The mechanisms of NIS regulation are multiple and not fully understood. However, it has been recently observed that some of the intracellular pathways involved in its regulation are over-activated in thyroid cancer [3-5].
A considerable number of cases of false-positive radioiodine uptakes have been reported in the Literature so far [6-8].
We herein reported on a case of false-positive 131I uptake in correspondence of a bronchocele, a segment of bronchus, usually dilatated, filled with mucus and completely enclosed . In addition, a summarized review of the Literature on this topic is also reported.
A 58 year old woman with a multinodular goiter underwent total thyroidectomy with incidental histological detection of multifocal follicular variant of Papillary Thyroid Cancer (PTC) in the left thyroid lobe (maximum size 0.7 cm), without infiltration of the perithyroidal soft tissues. TNM classification  was pT1a (m), Nx, Mx.
Upon subsequent RAI with 2.59 GBq of 131I uptake was detected in correspondence of the thyroid remnant, the thyroglossal duct and in the left hemithorax (Figure 1), in the absence of detectable serum Thyroglobulin (Tg) but positive anti-Tg Antibodies (TgAb). In order to investigate the pulmonary uptake of uncertain origin, a chest Computed Tomography (CT) was performed, which revealed multiple acinar opacities associated with thickening of the peripheral bronchi in both lungs (Figure 2), as well as in correspondence of the previously observed areas of WBS uptake.
Figure 1: Therapeutic WBS during withdrawal of LT4 therapy, 4 days after the first radioiodine treatment. WBS images revealed a round-shaped masslike lesion uptake in the left hemitorax.
Figure 2: Chest CT with contrast medium performed in February 2014. Enhanced CT demonstrated multiple acinar opacities associated with thickening of the peripheral bronchi in both lungs subsequently interpreted as bronchoceles.
During a second RAI, undetectable Tg and positive but decreasing TgAb were confirmed, but the WBS again revealed the same uptake in the left hemithorax.
A new CT study confirmed unchanged lung lesions supposed to be bronchoceles, which showed an uptake (SUV 8.17) at the following 18F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT) (Figure 3).
Figure 3: FDG-PET/CT performed in October 2015 during rhTSH stimulation test. The FDG accumulative bronchoceles was shown on the PET fused with low-dose nonenhanced CT images.
The patient thus underwent a Broncho-Alveolar Lavage (BAL), which revealed the presence of inflammation/infection, compatible with the suspicion of bronchocele and explaining the FDG-PET/CT result.
The patient was then strictly followed up, with persistence of TgAb positivity during suppressive L-T4 therapy and after stimulation, without any sonographic evidence of locoregional recurrence.
The ability to trap iodine is a unique feature of thyroid tissue. However, a variety of pathologic lesions have been reported to cause false-positive 131I uptake at WBS and, opposed to contrary to physiological uptake, they can create diagnostic misinterpretation.
Several cases of unexpected radioiodine uptake have been reported in Literature [6-8], in particular cystic (ovarian, breast and pleuropericardial), inflammatory and non-thyroidal neoplastic diseases. Interestingly, only one other case of bronchial mucocele with a scintigraphic uptake was described so far .
Although the mechanisms of these false-positive uptakes is not fully understood, in a recent review by Oh and Anh  this phenomenon was categorized as follows: 1) functional NIS expression in normal tissues or in different benign and malignant tumors, 2) metabolism of radioiodinated thyroid hormone, 3) retention of radioiodinated body fluids associated with or without structural change, 4) retention and uptake of radioiodine in inflamed tissues, 5) contamination by physiologic secretions, and 6) unknown.
In particular, points 3 and 4 of this classification could explain the case described in this paper. In fact, physiological dilatation of ducts such as a bronchus, regardless of the presence of obstruction, causes retention of body fluid containing radioiodine [6,12,13]. Moreover, considering that tracheobronchial secretions contain radioiodine, the presence of a bronchial obstruction, such as bronchocele, can result in positive radioiodine uptake which mimics metastatic involvement of DTC .
With regards to the point 4, in inflamed the occurrence tissues of hyperaemia, vasodilation, local edema and increased capillary permeability can result in a stasis of radioiodinated blood and in retention of radioiodine in leukocytes, which induce iodide organification as part of their bactericidal effect [6,14-18].
Finally, secretion of mucin containing iodide salts has also been suggested as another possible mechanism of iodine accumulation associated with chronic inflammatory conditions in mucocele [12,19,20].
Therefore, there are pitfalls in 131I WBSs interpretation, and, regrettably, there is a tendency to consider any localized 131I accumulation as metastatic localization of thyroid cancer, especially when located outside the neck. Some false positive can be ruled out easily. Contamination of skin, hair and garments by physiological secretions should be avoided by removing clothes and carefully washing skin and hair. Accumulation of iodine in the esophagus or gastrointestinal tract can be avoided by drinking water. The major diagnostic problems are constituted by false positive accumulations projecting in areas where thyroid cancer may metastasize, such as lungs and bones . Clinicians should especially consider a possible false positive uptake in case of discordant serum Tg or clinical history (low-risk thyroid cancer, complete surgical removal, previous negative imaging). To recognize the exact localization of radioiodine uptake and to reduce the incidence of false-positives in planar WBS, additional views (obliques), CT or MRI scan, and/or Single Photon Emission Computed Tomography/CT (SPECT/CT) [22-24] are recommended, so as to avoid unwarranted treatment. Although these are not common findings, false positive radioiodine uptakes should be suspected in presence of biochemical data and imaging finding negative for recurrence of disease. In these cases, the measurement of Tg and other imaging studies are useful to avoid unnecessary therapy .
Therefore, the correlation of the scintigraphic finding with the anatomical imaging, the available biochemical data, the clinical history, and the physical examination are mandatory , and could decrease the possibility of misinterpretation of the WBS images, thus avoiding further improper staging, unnecessary administration of radioactive iodine, improper management, emotional stress and superfluous financial burden .
- Wartofsky L, Nostrand DV. Thyroid Cancer: A Comprehensive Guide to Clinical Management. Totowa: Humana Press. 2006.
- Ahn BC. Sodium iodide symporter f for nuclear molecular imaging and gene therapy: from bed-side to bench and back. Theranostics. 2012; 2: 392-402.
- Vaisman F, Carvalho DP, Vaisman M. A new appraisal of iodine refractory thyroid cancer. Endocr Relat Cancer. 2015; 22: 301-310.
- Vidal AP, Andrade BM, Vaisman F, Cazarin J, Pinto LF, Breitenbach MM, et al. AMP-activated protein kinase signaling is upregulated in papillary thyroid cancer. Eur J Endocrinol. 2013; 169: 521-528.
- Phay JE, Ringel MD. Metastatic mechanisms in follicular cell-derived thyroid cancer. Endocr Relat Cancer. 2013; 20: 307-319.
- Oh JR, Anh BC. False-positive uptake on radioiodine whole-body scintigraphy: physiologic and pathologic variants unrelated to thyroid cancer. Review Article. Am J Nucl Med Mol Imaging. 2012; 2: 362-385.
- Glazer DI, Brown RK, Wong KK, Savas H, Gross MD, Avram AM. SPECT/CT evaluation of unusual physiologic radioiodine biodistributions: pearls and pitfalls in image interpretation. Radiographics. 2013; 33: 397-418.
- Shapiro B, Rufini V, Jarwan A, Geatti O, Kearfott KJ, Fig LM, et al. Artifacts, anatomical and physiological variants, and unrelated diseases that might cause false-positive whole-body 131-I scans in patients with thyroid cancer. Semin Nucl Med. 2000; 30: 115-132.
- Ramsay BH, Byron FX. Mucocele, congenital bronchiectasis, and bronchogenic cyst. J Thorac Surg. 1953; 26: 21-30.
- American Joint Committee on Cancer: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al. editors. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer. 2010; 87-96.
- Lee WH, Park JM, Kwak JJ. A solitary large radioiodine accumulative lung lesion in high-dose 131I therapeutic scan: bronchial atresia with mucocele. Clin Nucl Med. 2015; 40: 149-152.
- Kienast O, Hofmann M, Ozer S, Dobrozemsky G, Dudczak R, Kurtaran A. Retention of iodine-131 in respiratory tract in a patient with papillary thyroid carcinoma after radionuclide therapy: a rare false-positive finding. Thyroid. 2003; 13: 509–510.
- Nair N, Basu S, Pakhale H. Unusual uptake of radioiodine in the chest in a patient with thyroid carcinoma. Br J Radiol. 2004; 77: 63–67.
- Jong I, Taubman K, Schlicht S. Bronchiectasis simulating pulmonary metastases on iodine-131 scintigraphy in well-differentiated thyroid carcinoma. Clin Nucl Med. 2005; 30: 688–689.
- Song HC, Heo YJ, Kim SM, Bom HS. Iodine-131 uptake in focal bronchiectasis mimicking metastatic thyroid cancer. Clin Nucl Med. 2003; 28: 351–352.
- Klebanoff SJ, Hamon CB. Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. J Reticuloendothel Soc. 1972; 12: 170–196.
- Regalbuto C, Buscema M, Arena S, Vigneri R, Squatrito S, Pezzino V. False-positive findings on (131)I whole-body scans because of posttraumatic superficial scabs. J Nucl Med. 2002; 43: 207–209.
- Brucker-Davis F, Reynolds JC, Skarulis MC, Fraker DL, Alexander HR, Weintraub BD, et al. False-positive iodine-131 whole-body scans due to cholecystitis and sebaceous cyst. J Nucl Med. 1996; 37: 1690–1693.
- Matheja P, Lerch H, Schmid KW, Kuwert T, Schober O. Frontal sinus mucocele mimicking a metastasis of papillary thyroid carcinoma. J Nucl Med. 1997; 38: 1022–1024.
- Duque JJ, Miguel MB, Ruiz E, Castillo L, Claver M, Rubio MJ, et al. False-positive I-131 whole-body scan in follicular thyroid carcinoma caused by frontal sinus mucocele. Clin Nucl Med. 2000; 25:137–138.
- Triggiani V, Giagulli VA, Iovino M, De Pergola G, Licchelli B, Varraso A, et al. False positive diagnosis on 131iodine whole-body scintigraphy of differentiated thyroid cancers. Endocrine. 2016; 53: 626-635.
- Garger YB, Winfeld M, Friedman K, Blum M. In Thyroidectomized Thyroid Cancer Patients, False-Positive I-131 Whole Body Scans Are Often Caused by Inflammation Rather Than Thyroid Cancer. J Investig Med High Impact Case Rep. 2016; 4: 2324709616633715.
- Oh JR, Byun BH, Hong SP, Chong A, Kim J, Yoo SW, et al. Comparison of 131I whole-body imaging, 131I SPECT/CT, and 18F-FDG PET/CT in the detection of metastatic thyroid cancer. Eur J Nucl Med Mol Imaging. 2011; 38: 1459–1468.
- Maruoka Y, Abe K, Baba S, Isoda T, Sawamoto H, Tanabe Y, et al. Incremental diagnostic value of SPECT/CT with 131I scintigraphy after radioiodine therapy in patients with well-differentiated thyroid carcinoma. Radiology. 2012; 265: 902-909.
Citation: Mele C, Samà MT, Bisoffi AA, Orsini F, Mauri MG, Marzullo P, et al. False-Positive Iodine Uptake in a Patient with Differentiated Thyroid Cancer: A Rare Case of Uptaking Bronchoceles. Annals Thyroid Res. 2017; 3(1): 89-91.