Rapid Progression of SETTLE Tumor with Micrometastasis

To the Editor, In March 2005 we submitted a case describing an 11year-old African-American boy with the first reported spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid found to have micrometastasis at initial presentation. As we previously described [1], SETTLE tumors arise from branchial pouch remnants or foci of ectopic thymic gland, and they primarily affect children and young adults. Originally believed to follow an indolent course, long-term follow-up has revealed that many of these patients develop late metastatic disease. Seven of 20 reported patients with SETTLE tumor developed metastasis to locations including lymph nodes, lung, vertebrae, and kidney. Based on the presentation of this 11-year-old boy with early metastatic disease, an aggressive behavior was predicted, and the patient was treated accordingly with postoperative chemotherapy. As a result of the rarity of this lesion, the uniqueness of this particular case, and the difficulty in treating such patients, we here describe his clinical progression since his initial presentation in June 2004. After surgical resection in October 2004, the patient was treated with 4 cycles of etoposide and cisplatin between December 2004 and February 2005, which he tolerated well. In September 2005, computed tomographic (CT) scan of the chest with intravenous contrast revealed a small 5-mm nodule within the left upper lobe. The lesion was followed by repeat CT in January 2006, at which time the lesion was noted to have increased in size to 1.2 cm. Elective lung wedge resection and pathologic evaluation confirmed metastatic SETTLE tumor. The now 13-year-old patient was placed on a chemotherapy regimen including etoposide, carboplatin, and ifosfamide, which he received from February until May 2006. Computed tomographic exam in August 2006 revealed more than 20 new pulmonary nodules, the largest of which measured 6 mm in diameter. On follow-up CT exam in October 2006, additional innumerable nodules were identified, and the previously noted nodules had increased in size. The lesions were considered to be consistent with metastatic disease. Additionally, a rounded soft tissue density is now present in the left paratracheal region adjacent to the original tumor site, and this lesion is also considered suspicious for recurrent SETTLE tumor. Unfortunately, this patient originally presented with micrometastatic disease and, as predicted, has rapidly progressed within 2 years time. Unlike a previously reported 12-year-old girl with metastatic disease after 1 year of delayed treatment [2,3], our patient displayed diffuse thyroid involvement by SETTLE tumor (as opposed to a nodular, circumscribed mass) and has not responded to chemotherapy treatment. In spite of postoperative chemotherapy and a 2nd round of chemotherapy after resection of a single pulmonary SETTLE lesion, this 13-year-old has developed multiple pulmonary nodules. In view of the potential for rapid progression in patients with SETTLE tumor, we recommend extensive pathologic sampling, and in cases presenting with lymphovascular invasion, lymph node metastasis, extrathyroidal extension, or infiltrative borders, adjuvant therapy as well as close long-term follow-up should be strongly considered.