A 20-year-old woman presented to the endocrinologist with an enlarged thyroid. The patient had no history of thyroid disease. On palpation, a firm right thyroid lobe nodule was detected, measuring 6 × 7 cm. No palpable lymph nodes were evident in the neck. Iodine-131 thyroid scintigraphy revealed a cold nodule in the right thyroid lobe. Thyroid function test results were normal; serum concentration of calcitonin and thyroglobulin were within the reference range. Fine-needle aspiration biopsy did not yield sufficient material for diagnosis.Right thyroidectomy was performed without lymph node dissection. Grossly, the thyroid lobe was almost entirely replaced by a firm nodule that measured 6 × 7 × 3 cm. The cut surface was white and lobulated by the fibrous capsule (Figure 1). Microscopically, the tumor was highly cellular and composed of sheets of spindle cells that formed intersecting or streaming fascicles separated by sparsely cellular stromal septa (Figure 2; hematoxylin-eosin, original magnification ×250) and partially circumscribed by a thick fibrous capsule. Small tubulopapillary epithelial foci were intermingled within the spindle cells (Figure 3; hematoxylin-eosin, original magnification ×400). Tumor cells lacked nuclear atypia and mitoses were rare (<2 mitosis per 10 high-power fields). Immunohistochemically, most of the tumor cells, including spindle type, were strongly positive for pancytokeratin (Figure 4; immunohistochemistry, original magnification ×400). The α-smooth muscle actin and vimentin were positive for a few spindle cells. Reaction to epithelial membrane antigen (EMA), desmin, thyroglobulin, calcitonin, and S100 protein were negative.What is your diagnosis?We report a case of spindle epithelial tumor with thymuslike differentiation (SETTLE) of the thyroid in a 20-year-old woman. The tumor located at the right lobe was well circumscribed by fibrous capsule. Microscopically, the highly cellular spindle cell neoplasm was arranged in intersecting fascicles separated by fibrous bands and was intermingled with small tubulopapillary epithelial foci. Immunohistochemically, most of the tumor cells were strong for pancytokeratin and focally positive for smooth muscle actin and vimentin. The cells were negative for EMA, thyroglobulin, S100 protein, and the diagnosis of thyroid spindle thymuslike differentiation was made.Thyroid SETTLE is a rare tumor seen exclusively in children, adolescents, and young adults.1 It presents as a painless thyroid or neck mass and exceptionally as a diffusely enlarged thyroid gland.The term SETTLE emphasizes the epithelial nature of the tumor and suggests its probable thymus line of differentiation.2 Grossly, SETTLE is partially encapsulated or infiltrative; the cut surface is firm and vaguely whorled.2 Histologically, the tumor is highly cellular, composed of masses of spindle cells separated by sclerotic bands of collagen. Spindle cells are arranged in sheets and short fascicles and blended with a few epithelioid cells arranged in tubules and tubulopapillary areas.3 Nuclear atypia and mitoses are rare. Squamous differentiation and remnants of Hassal corpuscle are rarely detected.4Both spindle and “epithelioid” cells are strongly and diffusely positive for pancytokeratin and focally for vimentin; they are negative for EMA, desmin, thyroglobulin, calcitonin, and S100 protein. The negative reaction for thyroglobulin and calcitonin exclude spindle cell variant of the medullary thyroid carcinoma and poorly differentiated thyroid carcinoma, respectively.2After immunohistochemistry, 2 lesions must be differentiated from SETTLE: ectopic cervical thymoma and synovial sarcoma. Ectopic cervical thymoma is composed of plump epithelial cells, often with a spindle shape, admixed with lymphocytes, which are usually absent in SETTLE.3 Synovial sarcoma, especially the monophasic variant, can also mimic SETTLE. However, in synovial sarcoma, spindle cells are more pleomorphic with more mitoses. Staining reaction with pancytokeratin is low or absent, in contrast to SETTLE. In addition, EMA positivity is regarded as a reliable marker of synovial sarcoma, being negative in SETTLE.3SETTLE must be considered a potentially malignant tumor with a possibility of developing late lymph node or pulmonary metastases,4 thereby justifying a correct diagnosis and strict supervision.
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