Introduction
The detection of a pulmonary nodule in patients who have papillary thyroid carcinoma (PTC) often presents us with a diagnostic dilemma because the lung is one of the most common sites of metastasis of PTC. However, primary lung cancer [
1] and benign disease entities, including nonspecific findings, can also coexist with PTC. Radioiodine scans and serum thyroglobulin (Tg) measurements are the most commonly used methods for monitoring patients with thyroid cancer [
2]. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is primarily used to detect recurrence or metastatic disease in patients who have negative findings with
131I whole body scan (WBS) and elevated Tg levels [
3].
Although the clinical value of FDG-PET for the follow up of patients with thyroid cancer remains controversial, its use is rapidly increasing in clinical practice due to concerns about recurrence or metastasis of thyroid cancer. Also, some studies have indicated that FDG-PET is effective in patients with undetectable Tg levels [
4,
5].
The detection by FDG-PET of a pulmonary nodule in patients with PTC, even those displaying undetectable stimulated Tg and negative 131I WBS, includes a considerable variety of entities, therefore the diagnosis must be made with caution. Although solitary metastasis to the lung from thyroid cancer is quite rare, metastasis from PTC can manifest as a solitary pulmonary nodule. However, clinicians should be aware of the possibility that pulmonary nodules mimicking metastasis on FDG-PET with computed tomography (CT) in patients who have PTC could be primary lung cancer.
We describe two patients who presented with pulmonary nodular lesions by FDG-PET-CT and unexpected results on histologic confirmation with no evidence for distant metastasis on serum-stimulated Tg and 131I WBS.
Discussion
When a pulmonary nodular lesion is present in a patient with post-surgical thyroid cancer with undetectable stimulated Tg levels, diagnosis and management of the nodule can be confusing.
The typical radiographic appearance of pulmonary metastases from PTC is a random distribution of multiple nodules [
6]. When a solitary nodule is present in patients with post-surgical PTC with negative
131I WBS and undetectable stimulated serum Tg levels, diagnosis of the nodule is likely to be primary lung cancer, not metastasis to the lung from PTC.
The first presented case represents a rare example of metastasis of PTC presenting as a solitary pulmonary nodule without a clinically suspicious metastasis. The patient initially posed a diagnostic problem because the lung mass was located in a site that was not easily accessible to biopsy. Therefore, we performed surgical resection for accurate diagnosis and treatment under an initial clinical impression of primary lung cancer.
Solitary metastasis to the lung from thyroid cancer is quite rare and 14 cases of a solitary pulmonary metastasis from thyroid cancer, including our case, have been reported [
7,
8]. Moreover, metastasis from micro-PTC has been reported in only five cases, including our case [
7]. Seven of the 14 cases initially presented as a solitary lung nodule without a known history of thyroid cancer, with the remainder detected during follow-up for PTC.
In general, serum Tg measurement and radioiodine WBS are recommended for the postoperative follow-up of PTC [
2]. However, metastatic diseases for which the ability to take up radioactive iodine is lost are possible. Nakada
et al. reported that two of four patients with a solitary pulmonary nodule on multidetector-CT were proven to be metastasis from PTC but neither showed positive radioiodine uptake. Moreover, seven of nine patients (78%) having pulmonary metastasis showed negative radioiodine uptake [
9].
CT using iodine-rich contrast material can affect the results of radioiodine WBS. However, we performed a chest CT scan after T4 withdraw of radioiodine WBS in both cases. Therefore, we think that the results of WBS were not affected by the contrast material of the chest CT scan.
For patients with non-iodine-avid disease, the detection of metastases may be delayed. Furthermore, it has been reported that stimulated serum Tg determinations most sensitively detect recurrence and metastasis. However, it should also be noted that even an undetectable stimulated Tg with negative Tg Ab, as in the present cases, does not exclude a metastatic focus.
Although more recent publications have provided data that support the use of FDG-PET scanning for indications beyond simple disease localization in Tg-positive, radioactive iodine scan-negative patients, the clinical application of FDG-PET in patients with thyroid cancer with stimulated Tg negative and radioactive iodine scan-negative are not recommended routinely. However, patients with cancer can receive medical costs benefits through the National Cancer Registration in Korea and costs of radiologic imaging studies are not expensive. Therefore, the use of FDG-PET-CT is rapidly increasing in real clinical practice in Korea. Wang
et al. reported a sensitivity of 79.3% for PET in patients with a negative iodine scan, compared with only 18.6% sensitivity in those with positive iodine scan [
10]. In the two presented cases, the pulmonary nodule in each patient was detected by chance. If we had not performed FDG-PET, detection of these nodules may have been delayed until other clinical clues developed.
The cause of a single metastasis in PTC is unknown. Although the mechanism is unclear, macronodular single metastatic foci and loss of capability in the uptake of radioiodine (functional loss of iodine uptake) is responsible for an evident worsening in prognosis.
However, as highlighted by the second case, pulmonary nodules in patients who have PTC can be primary lung cancer. Although the results of 131I WBS and serum Tg were negative, several nodules of lung were thought initially to represent a metastatic PTC due to a typical finding for metastasis of PTC. However, pulmonary nodular lesions were identified as pulmonary adenocarcinoma through PTNB and TBLB. In general, because primary lung cancer carries a poorer prognosis than PTC, if physicians consider multiple lung nodules as metastatic PTC, then inappropriate treatment may worsen prognosis.
The accurate diagnosis of a pulmonary nodule in patients with PTC is important in the choice of the optimal treatment. Radioactive iodine has been the mainstay of treatment for patients with distant metastases; young patients having iodine-avid pulmonary micrometastases achieved remission rates of 90% at 10 years [
1]. However, for patients with metastatic disease for which the ability to take up radioactive iodine is lost, survival is poor (5-year and 10-year survival rate of 29% and 10%, respectively) [
11]. A study by Casara
et al. reported that the oldest patients (mean age 61.9 years) showed a tendency of nonfunctioning and macronodule metastasis. For patients with pulmonary metastases that are large or nonresponsive to radioactive iodine, surgical resection can be considered [
11].
The challenging issue in differentiated thyroid cancer is that there are patients with metastatic disease who can lose their radioiodine uptake and have negative stimulated serum Tg. A pulmonary nodule detected by FDG-PET in patients with PTC even showing negative for both stimulated serum Tg and 131I WBS includes a considerable variety of entities. Thus, a diagnosis must be made with caution.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
CHJ and JOM contributed to patients’ diagnosis and treatment. HJG and BYK participated in the literature review. JMP and HSH contributed to radiology-related issues and JJK contributed to histology-related issues. CHK and SKK participated in interpretation of the case. All authors read and approved the manuscript.