Chest wall lymph node metastasis from follicular thyroid carcinoma: a rare case report

Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer subtype after papillary thyroid cancer (PTC), and it accounts for approximately 10% of all thyroid cancers [1]. The average prognosis of FTC is worse than that of PTC [2]. Follicular thyroid cancer is known to metastasize hematogenously, which could explain its more common distant spread compared with papillary thyroid cancer [3]. The incidence of distant metastasis in FTC has been reported to be 6–20% [4‐6]. The bones and lungs are the most frequent sites of distant metastases. However, metastases can also occur in some unusual sites (e.g., the parotid gland, skin, brain, ovary, adrenal gland, kidney, pancreas, breast and eye) [3]. Cervical lymph node metastases at diagnosis are significantly less common in follicular thyroid cancer than in papillary thyroid cancer, with an incidence of 2–8% [7, 8]; this rate increases to 17% when widely invasive follicular thyroid cancer is considered [9]. However, distant lymph node metastases have been reported sporadically, with a few reports of axillary lymph node metastases [10, 11]. This study contributes to the literature one additional case of chest wall lymph node metastasis from follicular thyroid carcinoma in a 69-year-old woman.

In March 2018, a 69-year-old woman with a history of follicular thyroid cancer presented with a 3-month history of masses in the left chest. She had undergone total thyroidectomy with right-sided cervical lymphadenectomy in our department and pathological diagnosis was thyroid follicular carcinoma (Fig. 1), followed postoperative iodine treatment 10 years previously. Two years later, the patient developed a recurrence of left cervical lymphadenopathy, for which she underwent left-sided modified radical neck dissection. Unfortunately, she experienced left supraclavicular and left axillary lymph node recurrence in 2013 and underwent a third operation to resect these metastatic lesions. Following the third iodine treatment, levothyroxine tablets were administered. Physical examination revealed solid, mobile, painless masses in the left chest wall, the largest of which was approximately 4 × 3.5 cm in size below the left clavicle; a medium-sized mass was found in the second intercostal space that was 2.5 × 2 cm in size, while the smallest mass was in the third intercostal space and measured 1 × 1 cm in size (Fig. 2). Ultrasonographic examination revealed hypoechoic lymph nodes. A computed tomography (CT) scan of the chest showed lymph node enlargement in the subclavian area, and no pulmonary metastases were found (Fig. 3). Systemic and local scans were performed 48 h after oral administration of iodine-131 5 mCi. There was no significant radioactive concentration in the thyroid region, but there was radioactive concentration under the left clavicle and increased point-like radioactive uptake in the left chest wall. Left subclavian and thoracic lymph node metastases of thyroid carcinoma were considered (Fig. 4). Cranial and abdominal CT and whole-body bone scans did not reveal further pathology. Laboratory test results revealed normal T4 and T3 levels, a thyroid-stimulating hormone (TSH) level of 2.5 pg/ml (normal < 10 pg/ml) and serum thyroglobulin (TG) level of 3000 ng/ml (normal < 50 ng/ml). Ultrasound-guided core-needle biopsy of the mass revealed a follicular thyroid neoplasm with lymph node metastases. The results of immunohistochemical analysis indicated TTF, CK7, and thyroglobulin positivity and partial CD56 positivity, while the test for CgA was negative; the Ki67 index was 5%(Fig. 5). Mass resection was performed on the left chest wall under local anesthesia. Multiple lymph nodes were found to be enlarged under the left clavicle, and a total of 4 lymph nodes were removed, with a maximum diameter of 3 cm. The second intercostal lymph node was 1.5 cm in diameter, and the diameter of the third intercostal lymph node was 0.6 cm (Fig. 6). The final pathological diagnosis was thyroid follicular carcinoma metastasis to the lymph node (Fig. 7). Following a I¹³¹ radiotherapy session, TSH suppression therapy was continued. Nearly 1 year after the last operation, the patient’s serum thyroglobulin level has remained below the threshold, and no local recurrence or distant metastasis has been observed.

Although follicular thyroid cancer is a relatively indolent differentiated thyroid cancer, distant metastasis may occur in some patients because it tends to invade blood vessels and metastasize by hematogenous spread to distant sites, most commonly to the bones and lungs, although other unusual sites such as the parotid gland, skin, brain, ovary, adrenal gland, kidney, pancreas, breast and eye have been reported in the literature. Cervical lymph node metastases are less common in follicular thyroid carcinoma, and distant lymph node metastasis is very rare. The pathophysiology of metastatic thyroid carcinoma to distant lymph nodes remains elusive [12]. However, the routes of metastatic chest wall tumors are commonly hematogenous, lymphogenous and diaphragmatic [13]. Cervical lymphatics are also in communication with mediastinal lymph nodes, and consequently, mediastinal lymph nodes are occasionally involved in thyroid malignancies [14, 15]. However, CT and iodine-131 whole-body scanning did not show any sign of mediastinal lymph node metastasis in this 69-year-old woman. Rouviere described the communication between cervical and axillary lymphatics in 1932 [16], reporting that the physiologic flow to the jugulo-subclavian junction is centripetal. This centripetal flow can change under certain circumstances, such as when sentinel nodes around the lymphatic terminus in the jugulo-subclavian confluence block lymphatic flow due to tumor invasion, surgical manipulation or radiotherapy. Then, a retrograde flow pattern follows along the transverse cervical lymph node in the supraclavicular region, finally leading to axillary lymph node metastasis. This finding is supported by a review of all known cases of thyroid carcinoma metastasis to the axillary lymph nodes, showing that extensive cervical metastases and/or previous neck dissection may favor lymphatic over hematogenous spread [12]. This finding is also supported by the fact that 2 to 9% of patients have died of other head and neck cancers with axillary node metastases [17, 18]. The natural lymphatic drainage of the patient was disrupted due to previous bilateral cervical dissection and axillary and supraclavicular lymph node dissection; then, the lymphatic flow changed to a retrograde pattern and moved through the subclavian to the chest wall. This may explain the observation of metastatic lymph nodes on the left chest wall that gradually decreased in size from top to bottom.

Survival in FTC cases is associated with older age at the time of diagnosis, larger tumor size, capsular invasion, male sex and the presence of distant metastases [19, 20]. The presence of distant metastases predicts a lower long-term survival [3] and often necessitates additional surgical intervention, external beam radiotherapy, endocrine therapy and radioactive iodine treatment. This finding was also supported by the results of the study by Victor Zaydfudim et al. [21], who queried the Surveillance, Epidemiology, and End Results registry for patients diagnosed with well-differentiated thyroid carcinoma between 1988 and 2003. Cases were stratified by age (< 45 vs ≥ 45 years) and pathology (papillary/follicular). Finally, in patients with FTC, lymph node involvement conferred an increased risk of death in both age groups (P ≤ .002). However, Eleonora Farina et al. [22] came to the opposite conclusion, suggesting that metastasis to rare sites does not always represent a negative prognostic factor for disease outcome. In fact, they can occur as single distant lesions, and if surgically resectable, their treatment can also lead to local disease remission. In the past 10 years, our patient with right FTC underwent four operations for lymph node metastasis in the contralateral neck, supraclavicular and axillary lymph nodes, plus the thoracic wall lymph node metastasis described in this case report. The final pathological results confirmed lymph node metastasis from follicular thyroid cancer. At the same time, she underwent several I¹³¹ radiotherapy sessions, as well as long-term TSH suppression therapy. Nearly 1 year after the last operation, no local recurrence or distant metastasis has been found.

With regard to the reason chest wall metastasis occurred, the failure to completely clean the small lymph nodes below the left clavicle when the upper and left axillary lymph nodes were removed for the third operation may be an explanation; this failure could have opened the possibility for subsequent metastasis to the chest wall. In addition, iodine treatment resistance may also occur. In the future, we should consider performing gene detection and the use of targeted therapy.

Distant lymph node metastasis from follicular thyroid cancer is very rare. This study is the first report of a case of follicular thyroid carcinoma metastasis to the chest wall lymph node. Active comprehensive treatment, as well as long-term follow-up management, should be provided for these patients.