Spindle Epithelial Tumor with Thymus-Like Differentiation (SETTLE): A Distinctive Malignant Thyroid Neoplasm with Significant Metastatic Potential

Abstract

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid believed to be derived from branchial pouch or thymic remnants and showing primitive thymic differentiation. Although this tumor is prone to develop delayed blood-borne metastases, the metastatic risk is unclear because the case reports in the recent literature had very short follow-up periods. We report one case, the oldest patient reported so far, who had been followed up until death. The 59-year-old man had an enlarged thyroid for all of his adult life, and presented with recent rapid enlargement of the thyroid. Neck exploration revealed a hard tumor in the right lobe, with adhesion to sternothyroid muscle. Histologic examination showed an invasive biphasic neoplasm traversed by sclerotic septa. Tight to loose fascicles of blandlooking spindly cells were intimately intermingled with tubulopapillary structures, diagnostic of the SETTLE. This patient developed left pulmonary metastases at 2 years and subsequently developed bilateral pulmonary and widespread metastases. He died 8 years after initial presentation. This case illustrates the protracted clinical course of the tumor, and survival for many years despite the occurrence of metastases. Review of the literature shows that SETTLE occurs predominantly in young patients with a median age of 15 years and male predominance. There is a significant metastatic rate of 71% for patients with more than 5 years of follow-up in spite of the otherwise indolent nature of the tumor.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review

“…In the literature, there are at least 4 patients who had the thyroid mass noticed for four or more years, which suggest a slow tumoral growth (5)(6)(7)(8).…”

“…Metastatic spread is reported to lung, mediastinum, local lymph nodes and kidney. The principal site of metastasis is the lung, which represents more than 60% of the metastasis sites (2,8,10,12,14). The gap between diagnosis and detection of metastasis varies from a few months after the primary tumor manifestation to 25 years (14,15).…”

“…In spite of the disease progression with metastasis development, low mortality rates are observed, demonstrating the indolent course of the tumor. SETTLE may not produce metastasis until many years after the diagnosis (mean of 11 years) and according to case reports with follow-up information, the overall rate of metastasis is of about 20% (2,(8)(9)(10)(12)(13)(14)(15). Otherwise, when the analysis is made only on patients with more than 5 years of follow-up, the incidence increases to 50% (8,(12)(13)(14) with 2 patients developing metastasis more than 20 years after the diagnosis (13,14).…”

“…Xu and Cheuk reported negativity for CD5 (which is expressed in high number of thymic carcinoma, including CASTLE) and for CD20 (which is expressed in high number of the spindle cells of spindle thymoma) (21,8). Cheuk and cols.…”

“…The two components of SETTLE are always negative for thyroglobulin, calcitonin, chromogranin A, synaptophysin, CEA, desmin and S-100 protein (2,6,8,16,18,21). Special care is required in cases with trapping of normal thyroid follicles, because when stained with thyroglobulin, the tumoral cells can stain positive due to overflow of the antibody (16).…”