Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis, often presenting at an advanced stage with metastatic spread1. ESCC is the predominant histological subtype of esophageal cancer, accounting for approximately 85% of cases worldwide2. Despite advances in diagnosis and treatment, the 5-year survival rate for ESCC remains low, ranging from 10% to 20%2.

Metastatic spread of ESCC to distant organs is a common occurrence, with the liver, lungs, and bones being the most frequently affected sites3. However, metastasis to the thyroid gland is extremely rare, estimated to occur in only 0.5-1.5% of thyroid metastases4, 5. Comprehensive reviews reveal that thyroid metastasis from ESCC typically presents in advanced-stage disease, with a median age of around 60 years and a slight male predominance6, 7. Previously reported cases of ESCC with concurrent thyroid and supraclavicular lymph node involvement are extremely rare. While there have been documented instances of supraclavicular lymph node metastasis in ESCC, specific cases involving both the thyroid and supraclavicular lymph nodes are limited8, 9, 10, making our case particularly unique. The mechanism of metastasis likely involves lymphatic spread, given the anatomical proximity and lymphatic drainage patterns between the esophagus and thyroid gland11. The proposed protective mechanisms of the thyroid include high oxygen saturation and iodine concentration of venous blood, which may hinder the adhesion and growth of tumor emboli12, 13, fast arterial flow impeding tumor adhesion14, and the thyroid capsule acting as a physical barrier15.

We report a rare case of advanced ESCC metastasizing to the thyroid and supraclavicular lymph nodes in a 68-year-old male. This case highlights the need for careful evaluation of unusual thyroid lesions to rule out secondary malignancies, especially in patients with a history of ESCC. It also demonstrates the necessity of comprehensive diagnostic workup and a multidisciplinary approach when assessing rare metastases. The aim of this report is to expand the limited evidence on this uncommon manifestation of ESCC and its aggressive course.

The case of a 68-year-old male diagnosed with advanced-stage primary ESCC with metastases to the left thyroid lobe and left supraclavicular lymph node is a rare occurrence, with thyroid metastases from distant primary tumors reported in only 1.4% to 3% of clinical series and up to 24% in autopsy studies16. The most common primary tumors metastasizing to the thyroid gland are renal cell carcinoma, lung cancer, and breast cancer17. Metastases from gastrointestinal tumors, including ESCC, to the thyroid gland are even rarer18.

Differentiating primary thyroid squamous cell carcinoma from metastatic ESCC is challenging and requires identifying the primary ESCC site5, 19. Although primary thyroid squamous cell carcinoma is rare, it should be considered in the differential diagnosis, particularly in patients with a history of smoking and alcohol consumption. In this case, the presence of a pharyngeal mass on imaging and endoscopy raises the possibility of hypopharyngeal squamous cell carcinoma extending to the thyroid gland, which is not uncommon. Immunohistochemistry was crucial, showing negative thyroid transcription factor-1 and thyroglobulin, confirming esophageal origin. In this case, several factors strongly suggest that the thyroid lesion is a metastasis from the primary ESCC, including the absence of thyroid follicular cells in the FNA sample, the patient's advanced-stage ESCC with confirmed metastasis to the left supraclavicular lymph node, and the rapid clinical deterioration and short survival time20, 21. Immunohistochemical markers, such as TTF-1, thyroglobulin, and PAX8, are useful in distinguishing between primary thyroid tumors and metastatic lesions22, 23. The absence of these markers in the present case further supports the diagnosis of metastatic ESCC to the thyroid gland.

The prognosis of patients with thyroid metastases from ESCC is particularly unfavorable24, with a reported median survival of 5-8 months4, 5. Early detection and close monitoring of suspicious thyroid lesions are crucial, and a high index of suspicion for metastatic disease should be maintained in patients with a history of ESCC presenting with thyroid nodules or masses. Prompt diagnostic workup and close collaboration between clinicians, radiologists, and pathologists are essential for accurate diagnosis and staging. There is no clear consensus on diagnostic criteria and management, but reported options include thyroidectomy, chemotherapy, radiation, or combined modalities, albeit with limited efficacy4, 5, 25. The choice of treatment depends on factors such as the primary tumor type, the extent of metastatic disease, and the patient's overall health and prognosis26. In cases of advanced-stage cancer with multiple metastases and poor performance status, as in the present case, palliative care may be the most appropriate approach to improve quality of life27.

The findings from this case have several important implications for clinical practice and future research. First, the presence of thyroid metastasis in ESCC may serve as an indicator of particularly aggressive disease requiring urgent intervention10. Second, the concurrent involvement of supraclavicular lymph nodes suggests a potential metastatic pathway that warrants further investigation28. From a diagnostic perspective, our case emphasizes the importance of comprehensive immunohistochemical analysis in distinguishing primary thyroid malignancies from metastatic disease29. Future research directions should focus on: (1) developing predictive models for unusual metastatic patterns in ESCC, (2) investigating the role of novel imaging techniques in early detection of thyroid metastasis, and (3) evaluating the efficacy of targeted therapies in such cases.

While genetic testing was not performed in this case due to rapid disease progression and limited clinical utility in the terminal stage, we acknowledge this limitation. Recent studies have identified several genetic alterations associated with ESCC metastasis, including mutations in TP53, PIK3CA, and NOTCH1 genes, as well as dysregulation of various molecular pathways such as WNT/β-catenin and PI3K/AKT/mTOR signaling30, 31, 32. Additionally, specific biomarkers like PTEN, STMN1, and TNFAIP8 have been linked to ESCC metastatic potential33. Future studies should aim to identify specific genetic alterations or biomarkers that may predict the risk of metastasis and guide personalized treatment strategies, particularly focusing on rare metastatic sites such as the thyroid gland34.

While our patient's rapid decline precluded active treatment, several therapeutic options merit consideration for similar cases. For isolated thyroid metastasis, surgical resection may be considered in selected patients with good performance status14. Systemic therapy options for metastatic ESCC include platinum-based chemotherapy combinations35. Recent advances in immunotherapy, particularly immune checkpoint inhibitors, have demonstrated promising results in advanced ESCC36. Palliative radiotherapy may provide local control and symptom relief, particularly for dysphagia37. The choice of treatment should be individualized based on patient factors, disease extent, and molecular profile when available.

The case report highlights the rare occurrence of metastatic esophageal squamous cell carcinoma (ESCC) in the thyroid gland and the diagnostic challenges it presents. The current case aims to raise awareness among clinicians about the possibility of ESCC metastasis in the differential diagnosis of unusual thyroid lesions, especially in patients with a history of ESCC. A comprehensive diagnostic approach, including imaging studies, fine-needle aspiration, and immunohistochemical staining, is essential for accurate diagnosis and staging. The aggressive nature of metastatic ESCC to the thyroid gland underscores the importance of early detection and close monitoring of suspicious thyroid lesions in patients with a history of ESCC. A multidisciplinary approach involving clinicians, radiologists, and pathologists is crucial for optimal patient management. This case emphasizes the need for heightened awareness among various clinicians beyond oncologists and endocrinologists, including general practitioners and head and neck surgeons, and highlights the necessity for future research in this area.

AJCC: American Joint Committee on Cancer, ESCC: Esophageal Squamous Cell Carcinoma, FNA: Fine-Needle Aspiration, MRI: Magnetic Resonance Imaging, NOTCH1: Notch Receptor 1, PET/CT: Positron Emission Tomography/Computed Tomography, PI3K/AKT/mTOR: Phosphoinositide 3-Kinase / Protein Kinase B (AKT) / Mammalian Target of Rapamycin, PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha, PTEN: Phosphatase and Tensin Homolog, STMN1: Stathmin 1, TFTs: Thyroid Function Tests, TNFAIP8: Tumor Necrosis Factor Alpha-Induced Protein 8, TP53: Tumor Protein p53, TTF1: Thyroid Transcription Factor-1, UICC: Union for International Cancer Control, WNT/β-catenin: Wnt Signaling Pathway / Beta-Catenin

None.

DVN and CTD conceived the study and participated in its design and coordination. DVN, HTD, THD, and DQV participated in data curation and investigation. DVN and CTD drafted the manuscript. HTD, THD, and DQV critically revised the manuscript for important intellectual content. CTD supervised the study and provided methodological guidance. All authors read and approved the final manuscript.

None.

Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

This case report was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The article is written according to the guidelines of the ethics committee of our institution. This case report was exempt from formal ethical approval at our institution as it involved only retrospective review of medical records and did not involve any direct patient contact or intervention. All patient information has been sufficiently anonymized to protect the patient's identity and confidentiality.

Written informed consent was obtained from the patient's next of kin for publication of this case report and any accompanying images, as the patient had passed away shortly after the diagnosis. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

The authors declare that they have no competing interests.