Isolated pulmonary metastasis occurring 10 years after total thyroidectomy and lymphadenectomy of a papillary thyroid carcinoma: a rare case report

Introduction

Papillary thyroid carcinoma (PTC) is the most common types of thyroid cancer; and the 10-year survival rate vary from 85% to 100% (1,2). Although the prognosis of PTC is favorable, the risk of recurrence ought not to be disregarded. A study found that the overall recurrence rate of PTC lies between 4.3% and 35% (3). It is notable that cases of PTC, with recurrence and metastasis after an extended period of time, occur predominantly in the cervical lymph nodes (4), and distant metastasis is rare.

This paper presents the case of a patient with PTC who developed pulmonary metastasis ten years after surgery. Although the majority of these tumors can be cured, for patients at risk of recurrence, such as those with a tumor diameter >4 cm and concurrent lymph node metastasis, etc. Providing I-131 treatment after surgery; taking levothyroxine sodium orally; and conducting regular re-examinations are effective measures for preventing recurrence and metastasis. The diagnosis of such patients was based on the combination of clinical history and relevant pathological examinations to avoid missed diagnoses and misdiagnoses. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-86/rc).

Case presentation

A 61-year-old female came to The Third Hospital of Mianyang with a recurrent cough accompanied by expectoration of over 4 months duration; and lung nodules which had been detected 5 days previously. Four months prior to admission, the patient had developed the cough following a cold. Initially, it had been accompanied by white, foamy sputum; however, it transformed thereafter into a yellow, sticky sputum. The patient visited the clinic and the local health center successively; and felt alleviated after receiving drug treatment (the details were unspecified). Subsequently, the previously mentioned symptoms recurred. The patient received long-term treatment with traditional Chinese medicine; however, no obvious alleviation of the symptoms was witnessed. Five days before coming to The Third Hospital of Mianyang, the patient had visited a local hospital of traditional Chinese medicine, and a chest computed tomography (CT) scan indicated a nodule in the lower lobe of the right lung. The patient then visited the Outpatient Department of our hospital for further diagnosis and treatment; and was admitted to the Thoracic Surgery Department for inpatient care with a diagnosis of “lung nodule”. Ten years previously, she had been diagnosed with a classical subtype of PTC involving both lobes (pT3aN1aM0), for which she had undergone a radical thyroidectomy, namely, total thyroidectomy combined with central compartment lymph node dissection and lateral cervical compartment lymph node dissection. The patient has lymph node metastasis in VI region, and the longest diameter of the largest metastatic focus is less than 3 cm. The thyroid hormone status of the patient prior to the operation remained unknown. Following the surgery, she had been taking levothyroxine sodium, at a dose of 75 µg orally, once a day for an extended period, without undergoing regular re-examinations. Upon admission, there were no palpable lesions in the neck. The chest CT scan in our hospital indicated the presence of an irregular, solid-density nodule in the posterior basal segment of the lower lobe of the left lung, measuring approximately 1.1 cm × 1.1 cm × 1.0 cm. The results of the enhanced CT scan indicate that the texture is heterogeneous, and there are marked differences in the degree of enhancement. The boundary was clear, featuring shallow lobulations and a few spiculated margins at the edge (Figure 1A). A positron emission tomography (PET)-CT scan revealed a nodular lesion in the posterior basal segment of the lower lobe of the left lung exhibiting an abnormally increased fluorodeoxyglucose (FDG) metabolism. It was considered that this was more likely to be a neoplastic than an inflammatory proliferative lesion. A biopsy was suggested for pathological confirmation (Figure 1B). In the cervical region of the patient, a hypoechoic structure is evident following the surgery. No nodules, masses, or foci of abnormally elevated FDG metabolism are observed in the surgical area. The cervical lymph nodes exhibit reactive hyperplasia. And the patient requested surgery for a definite diagnosis. The thoracic surgeon of our hospital submitted a sample of lung tissue from the patient for intraoperative frozen pathological examination. Cancer of thyroid origin was identified. Subsequently, a lung wedge resection and regional lymph node dissection were executed clinically. The gross finding of the routine pathological examinations indicated a grayish-white nodule within the lung parenchyma. This nodule presented with a grayish-white, solid, and moderately firm-cut surface; and an indistinct boundary. Upon microscopic examination (Figure 2A), the tumor cells exhibited the characteristics of PTC: they were densely arrayed, with enlarged and elongated nuclei presenting a ground-glass-like appearance and irregular nuclear membranes. Nuclear pseudo-inclusions were discernible; slender and branched papillary structures could be recognized; and the tumor cells in the surrounding alveolar cavities were diffusely distributed in nest-like aggregations. Tumor cells could also be observed in distant lung tissue. Immunohistochemistry revealed that these tumor cells were positive for TTF-1, CK7, and PAX8; negative for NapsinA and CgA; and positive for Galectin-3 and HBME-1 (Figure 2B). No mutation of the BRAF V600E gene was detected; and no lymph node metastasis was identified. During the preoperative reevaluation, serum levels of thyroid hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), were all within normal reference ranges. The TSH level was measured at 3.3 mIU/L. The final pathological diagnosis was: PTC with recurrence and metastasis.

Figure 1 The CT and PET-CT manifestations of the pulmonary space-occupying lesion. (A) An irregular solid density nodule is detectable in the posterior basal segment of the lower lobe of the left lung, approximately 1.1 cm × 1.1 cm × 1.0 cm in size. The enhanced scan reveals uneven and prominent enhancement. The boundary is distinct, with shallow lobulation and a few spiculated margins at the edge. (B) The manifestations of the pulmonary space-occupying lesion (the area indicated by the red arrows). The nodular lesion situated in the posterior basal segment of the lower lobe of the left lung displays abnormally augmented FDG metabolism, indicating the high probability of a neoplastic lesion. CT, computed tomography; FDG, fluorodeoxyglucose; PET, positron emission tomography.

Figure 2 The HE morphologies (200×) and the immunohistochemical staining (200×) of the tumors. Immunohistochemical staining was performed using the EnVision method (Zhongshan Jinqiao Biotechnology Co., Ltd., Beijing, China). (A) The HE morphologies (200×) of lung tumors. Microscopically, the tumors exhibit the characteristics of PTC. The nuclei are enlarged, elongated, and densely arranged. Ground-glass-like nuclei, irregular nuclear membranes, and intranuclear pseudo-inclusions are observable. Furthermore, slender and branched papillary structures are discernible; and the tumor cells in the surrounding alveolar cavities are diffusely distributed in nest-like clusters. (B) The tumor cells exhibit diffuse and intense positive staining of galectin-3 on the cell cytoplasm (left). The tumor cells exhibit diffuse and intense positive staining of HBME-1 on the cell membrane/cytoplasm (right). HE, hematoxylin and eosin; PTC, papillary thyroid carcinoma.

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Third Hospital of Mianyang (No. 2025-01). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Globally, thyroid cancer represents the most prevalent malignant tumor within the endocrine system, with an annual occurrence of as many as 586,000 new cases (5). The number of women surpasses that of men, ranging approximately from twofold to fourfold of the male count (6). Approximately 90% of patients afflicted with thyroid cancer present with differentiated thyroid carcinoma (DTC), encompassing two pathological subtypes: PTC (constituting 70–75%); and follicular thyroid carcinoma (FTC) (accounting for 15–20%) (7).

The most commonly identified mutation in PTC is BRAF V600E (8). Patients with thyroid cancer with BRAF mutations are activated by the V600E mutation in the BRAF oncogene, which leads to uncontrolled cell cycle progression and tumor growth. Previous meta-analyses indicated that the BRAF V600E mutation was associated with an increased recurrence rate of PTC (9). And BRAF mutation can serve as an accurate marker for diagnosis and decision-making with great value (10). Notably, in this particular case, no BRAF mutation was identified in the patient. The case suggests that patients without detectable BRAF V600E mutations remain at risk for recurrence.

In light of the prognosis of thyroid cancer, the American Thyroid Association (ATA) has advanced risk stratification for patients with DTC into low-, intermediate-, and high-risk groups (11). The recurrence rate among high-risk patients can exceed 20%, while that among intermediate-risk patients varies from 5% to 20% (12). Initial therapy is advocated for patients at high-risk (12). In this case, the patient was classified as intermediate-risk according to the ATA risk stratification guidelines, and therefore, I-131 therapy is considered to be controversial.

Siraj et al. conducted an analysis of the temporal variation in the tumor recurrence risk rate among 1,201 unselected Middle Eastern patients with PTC. The results revealed that for intermediate-risk PTC patients, the recurrence risk in the group without I-131 treatment was significantly higher than that in the group receiving I-131 treatment (2.3% versus 0.7%; P=0.0001) (13). In this case, the patient did not undergo postoperative I-131 therapy. And the risk of disease recurrence might be substantially elevated. The above findings suggest that for patients with intermediate-risk PTC, I-131 therapy should also be carried out following surgery to prevent the recurrence of the disease condition.

Garg et al. (14) performed a postoperative follow-up of 438 patients with DTC. Their research findings demonstrated that when the maximum diameter of the primary lesion exceeded 4 cm, the recurrence rate of the tumor was higher. In this instance, the diameter of the patient’s primary tumor was greater than 4 cm and may have been one of the risk factors for metastasis. DTC demonstrates a low degree of malignancy and a low fatality rate. Twenty to ninety percent of patients with DTC exhibit cervical lymph node metastasis at the time of diagnosis. The common site of distant metastasis is the lung (15). Hei et al. conducted a study on the clinical data of 1,140 patients who had undergone resection of PTC and found that 2.3% of PTC patients developed lung metastasis (16). Hakim Tawil et al. enrolled a total of 486 patients with PTC who had undergone thyroid surgery, and carried out a 10-year follow-up study. The research findings indicated that the recurrence rate of these patients was 9.6%, and the mean recurrence time was 3 years (17). The present therapeutic modality, incorporating Surgery (12), initial therapy, and TSH-suppression, is recommended by the ATA and the National Comprehensive Cancer Network (NCCN) for the management of DTC (18).

In the management of PTC, TSH suppression therapy serves as a crucial strategy for minimizing the recurrence risk. A previous study has indicated that an elevation in the level of TSH may be correlated with an augmented risk of recurrence in PTC (19). When patients continuously take levothyroxine after surgery, a TSH level exceeding 0.2253 mIU/L can be considered as a potential risk factor for tumor recurrence (20). In this study, the patient’s TSH level was 3.3 mIU/L, suggesting a relatively high risk of recurrence of PTC. Despite the patient’s continuous and regular administration of levothyroxine therapy post-operation, the TSH level was not routinely monitored. It was not until the recurrence of the disease that this issue was detected. Evidently, routine surveillance of TSH levels holds substantial significance for the long-term management of the disease and the monitoring of its recurrence.

Lymph node metastasis of PTC is relatively common; however, distant metastasis to organs like the lungs many years after surgery is infrequent. Hence, patients with metastatic foci as the initial manifestation are prone to misdiagnosis and missed diagnosis. Besides, PTC pulmonary metastases typically present as miliary or multiple nodular patterns on imaging studies (21). Solitary pulmonary metastasis of PTC is a rare clinical entity that often mimics pneumonia or primary pulmonary tumor. In our patient, a preoperative clinical diagnosis of primary pulmonary neoplasm was made based upon the patient’s history, physical examination, and imaging. The patient had no physical examination findings, nor imaging findings that would have led us to suspect his lung mass was anything other than a primary pulmonary malignancy. The main clinical manifestations, in this case, however, were cough and expectoration; and the patient’s chest CT indicated a solitary pulmonary nodule. Both the clinical and imaging manifestations lacked specificity (22). Therefore, for the diagnosis, differentiation from primary lung tumors was necessary; necessitating referral to the clinical history and pathological examination. This is one of the few instances in which a diagnosis of metastatic PTC was made following resection of a solitary lung mass. Given the absence of evidence indicating tumor recurrence or metastasis in other regions and the metastatic lesion has been completely resected, our patient scheduled to continued oral administration of levothyroxine sodium is necessary to maintain TSH levels within the lower limit (<0.1 mIU/L) of the normal reference range, with regular follow-up and monitoring recommended.

Conclusions

In conclusion, although the overall prognosis of PTC is favorable, it is crucially important that patients undertake a risk assessment for disease recurrence; attend regular re-examinations after surgery, particularly the TSH level; and TSH-suppression. Moreover, an active combination of I-131 initial therapy treatments, based on the risk level classification, is essential for the prevention of disease recurrence and metastasis. Where patients manifest with recurrence and metastasis, it is important that physicians integrate clinical history and the results of pathological examinations to prevent missed diagnoses and misdiagnoses. Based on this case, during the pathological diagnosis process: if the HE morphology of the lung tumor differs from that of typical primary epithelial-derived tumors, not only special types of cancers should be considered, but also the possibility of metastatic cancer. Attention should be paid to the patient’s past medical history, and finally, an accurate diagnosis may be made through immunohistochemistry and other auxiliary examinations for further verification. We hope this case will be helpful in the management and treatment of metastatic PTC in the future.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-86/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-86/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-86/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Third Hospital of Mianyang (No. 2025-01). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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