CASTLE is a rare disease of unknown etiology, accounting for 0.1–0.15% of all thyroid gland cancer. It commonly occurs among around 40 to 50 years old, and had a slight female predominance. It was first described by Miyauchi et al. in 1985 named “thymus carcinoma in the thyroid”. In 1991, Chan and Rosai separated the concept of this type of tumor into four groups: ectopic hamartomatous thymoma, ectopic cervical thymoma, spindle epithelia tumors with thymic-like differentiation – SETTLE and Carcinoma showing thymus-like elements – CASTLE. SETTLE and CASTLE show characteristics of malignant tumors, the other two pathologies were considered as benign tumors. SETTLE commonly occurs among the young, while CASTLE is more common at the ages of 50 2,3.
The histopathology and immunohistochemistry of tumor show features similar to thymus carcinoma cancer and possibly initial origins in thymus gland or branchial pouch. Immunohistochemical test showed CD5-positive characteristics in most cases, and negative with thyroid gland markers such as thyroglobulin and calcitonin. Molecular analysis shows p63-positive on most tumors of thymus origin, but negative results were found on cystic carcinoma and poorly differentiated form in thyroid gland4.
CASTLE is clinical indolent growth and favorable prognosis. Most patient came with a painless, slowly-growing mass in neck (especially the lower lobe of thyroid gland). Some patients may also experience hoarseness or swallowing due to the tumor’s invasion of neighboring soft tissue and regional lymph node. Other symptoms include dry cough and short of breath5. Our patient after initial total thyroidectomy and following up, until the recurrence of slowing growing cervical lymph node; the lymph node enlarged gradually over 3 years, making a compression at the time of recurrence. It has been reported that CASTLE can metastasize to the brain, liver and lungs at a very low rate6.
CASTLE arises in thyroid gland or the soft tissue of the neck. It is necessary to differentiate CASTLE from the other tumors such as primary or metastatic head and neck squamous cell or carcinoma of thyroid gland, because the prognosis and treatment therapy are different. Diagnostic imaging methods include neck ultrasound, head and neck CT scans and MRI. CASTLE tumors on head and neck CT scans often show an unclear boundary and no calcification lesion. Fine needle aspiration plays an important role in the diagnosis of thyroid cancer, especially papillary thyroid cancer, with the specific and sensitive rates of more than 90%. However, cytology cannot differentiate CASTLE from less differentiated thyroid cancer such as squamous carcinoma or undifferentiated thyroid carcinoma4,7. A needle biopsy can obtain a tissue samples with the appropriate size for immunohistochemistry. The IHC analysis shows a tumor that is strongly positive with CD5, p63, and cyto-keratin as well as negative with thyroglobulin, TTF1, and calcitonin5,8. Positiveness with CD5 marker helps to differentiate CASTLE from other tumors of the thyroid or respiratory tract – upper gastrointestinal tract9. Our case also showed similar results on pathology and IHC analyses: lesion positive with CK5, CK7, p63, C-kit and CD5 but negative with TTF-1, Thyroglobulin, GATA3, ER, CD99 and NKX2.2 (Fig. 3).
Due to the rarity of the disease, there are currently no standard treatment guidelines, but surgery is usually the first choice. According to the reports, the rates of extracellular invasive tumors and lymph node metastases are relatively high, at 50–60% and 50% respectively1,10,11. It í also reported that patients receiving curative surgery including total thyroidectomy and cervical lymph node dissection had favorable results, with regional recurrence rates of 14%, and 5 years and 10 years survival rates of 90% and 82% respectively12. Therefore, complete resection of the tumor, including removal of invasive organs, is essential to reduce rates of local recurrence and improve survival rates. CASTLE is considered as a disease that has good response to radiotherapy7. In one of Hidemitsu’s literatures, one patient refused surgery and was treated with radiotherapy only; after that, the tumor got a complete response, the following up for 7 years on CT scan did not show any recurrence. In addition, according to a study of 10 CASTLE patients undergoing surgeries (of that, 9 patients with a breaking thyroid tumor) and adjuvant radiotherapy, only 4 patients were witnessed recurrence and all of them were outside the irradiation areas10. It was suggested that patient with CASTLE should undergo surgery to completely remove tumors following by adjuvant radiotherapy. Also, some authors suggested that postoperative radiotherapy should be considered for patients possessing or suspecting positive lymph node. As reported by Roka and Piacentini, surgery was sufficient for patients who did not have lymph node metastases, as none of those patients had relapsed1,13. In Hidemitsu’s study, 2 patients who had no lymph node metastases and did not take postoperative radiotherapy, were followed up for 5 years and 10 years with no recurrence. According to the study of Sun et al., it rarely recurred after lymph node removal at initial surgery with negative pathology results11. For patients recurring after the initial treatment, surgery and radiotherapy still play an important role than chemotherapy. Some reports indicated the lower rates of local recurrence in the group of patients who had locally invasive widespread tumors and cervical lymph node metastases treated with radiotherapy10. Base on data reported, through multi – specialist consultation, maximal tumor removed surgery and adjuvant radiotherapy were chosen.
However, in our case, patient and her family later decided not to receive treatment and was discharged. At present, after 15 months follow-up the patient was stable, mainly discomfort because of tumor compression and palliative care after tracheostomy and tracheal stent.