Metastases from other organs to the thyroid are extremely rare, with cases mainly observed in autopsies.¹⁾ At autopsy, the breast and lung are the most common primary cancer sites that metastasize to the thyroid.^2,3)

Anaplastic thyroid cancer, the most aggressive form of thyroid malignancies, exhibits a broad spectrum of morphological features and can be difficult to diagnose due to a high degree of reverse differentiation. Unlike papillary and follicular carcinomas, which have been well differentiated, anaplastic thyroid cancer shows rapid growth and a high local recurrence rate, with a 5-year survival rate of 1.0-7.1%. The average survival time is reported to be 4 to 12 months.^4-6)

This report presents a case of thyroid anaplastic carcinoma diagnosed though fine needle aspiration (FNA) in a 76-year-old patient previously diagnosed with non-small cell lung carcinoma (NSCLC).

A 76-year-old woman with no respiratory symptoms or smoking history was admitted to the Department of Respiratory Medicine with a right lower lung mass found in chest PA detected on physical examination. Based on bronchoscopy performed for the evaluation of the lung mass, lung cancer was suspected and computed tomography (CT)-guided percutaneous core needle biopsy (PCNB) was performed. Positron emission tomography (PET)-CT imaging was performed before surgery to evaluate another metastasis (Fig. 1). The patient subsequently underwent a right lower lobectomy in the Department of Cardiothoracic Surgery, with the results of the postoperative histological examination indicating adenocarcinoma exhibiting acinar (40%), papillary (30%), and solid (30%) patterns (Fig. 2A).

In addition to the management of NSCLC, the patient was followed by thyroid ultrasound of two benign thyroid nodules since 2016. During the postoperative follow-up after thoracic surgery, 4-years later, the patient was referred to Department of General Surgery for elevated carcinoembryonic antigen (CEA) and increased size of the right thyroid nodule. FNA of the thyroid nodule indicated anaplastic carcinoma. Total thyroidectomy with central neck dissection was performed. The results of the histopathological examination indicated metastatic adenocarcinoma of lung origin with poor differentiation, which is clinically a very rare occurrence (Fig. 2B). Blood tests performed before surgery showed the following findings: tumor marker CEA 39.59 ng/mL, calcitonin 83 pg/mL, free thyroxine 1.14 μg/dL, free triiodothyronine 1.38 μg/dL, thyroid-stimulating hormone (TSH) 0.98 μIU/mL, anti-thyroglobulin antibodies 9.56 U/mL, parathyroid hormone 36.81 ng/L, and thyroglobulin 31.09 µg/L. No distinguishing biochemical features generally observed in anaplastic thyroid cancer were detected, such as the lack of thyroglobulin production, the inability to carry iodine, or the lack of TSH receptors.

The patient was subsequently seen in the Department of Respiratory Medicine for treatment of the cancer of pulmonary origin. The thyroid tissue was tested for epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK), and programmed death-ligand 1 (PD-L1) in the primary lung tissue (Table 1). PET-CT imaging performed after thyroid surgery detected multiple lymph node metastases, with hypermetabolism in right level IIB, III, IV, and VI border zone lymph nodes. However, no significant lymphadenopathy was observed on neck CT performed before thyroid surgery, as mentioned earlier. Brain MRI showed no metastatic lesions or specific findings, and chest CT detected no abnormalities in either of the neck lymph nodes.

Based on the mutations detected through additional genetic testing performed following total thyroidectomy, we initiated treatment for NSCLC recurrence using gefitnib (an EGFR inhibitor) based on Exon21 L858R mutation.

Despite the rich vascular supply to the gland, metastases to the thyroid are extremely rare,⁷⁾ accounting for less than 4% of all malignant thyroid tumors.^1,8)

Anaplastic thyroid cancer is a highly malignant disease. Due to its aggressive nature (which distinguishes it from other thyroid cancers), it is unlikely to be misdiagnosed as another disease. A cancer that has metastasized to the thyroid gland may be difficult to distinguish histologically from an undifferentiated cancer. This can be the case in situations in which the cancer transferred to the neck exhibits dedifferentiation, as in the reported case.

According to the National Comprehensive Cancer Network (NCCN) guidelines, lung cancer is classified into “small cell lung cancer” (15%) and NSCLC (85%) according to the histological features. NSCLC is further subclassified into adenocarcinoma (40% of NSCLC cases), squamous cell carcinoma (30%), or large cell carcinoma. Differentiation between squamous cells and the non-squamous epithelium has important connotations for the treatment of NSCLC. In many cases of non-squamous cell carcinoma, including adenocarcinoma, an induced mutation (driver mutation) is observed in EGFR, ALK, ROS1, or BRAF genes. It is important to test for these mutations, particularly EGFR and ALK, in all cases. When such mutations are found, drug treatment appropriate for the specific mutation should be selected. If mutations are not present, the PD-L1 test should be performed to determine whether single agent immunotherapy, combination immunotherapy, or a combination of immunotherapy with chemotherapy should be implemented, depending on the degree of expression.

Adenocarcinoma is the most common histological type found in patients with lung cancer, which has metastasized to the thyroid, with histological types associated with different life expectancies. While mutations in the EGFR and EML4-ALK genes are associated with thyroid metastases, the exact mechanism underlying this interaction has not yet been elucidated.