Case 5 -

Thyroid, Thyroidectomy – Spindle Epithelial Tumor with Thymus-Like Differentiation ("SETTLE") Juan Rosai Centro Diagnostico Italiano Milano, Italy

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Clinical History 36-year-old male with painless mass in the right side of the neck, clinically thought to be in the thyroid gland. The patient was euthyroid and there was no cervical lymphadenopathy. There was no family history of thyroid carcinoma. A total thyroidectomy was carried out. Grossly, there was a 3,5 x 2,5 x 3 cm mass that protruded under the thin transparent capsule of the right thyroid lobe. It was solid, lobulated, well-circumscribed but not encapsulated, with a white-to-yellow cut surface. The left thyroid lobe was unremarkable. Case 5 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 Case 5 - Figure 6 Case 5 - Figure 7 Case 5 - Figure 8 Case 5 - Figure 9 Description and Differential Diagnosis The tumor is composed of predominantly spindle cells with a monomorphic appearence, scanty mitoses, and no necrosis. The tumor is adjacent to the thyroid gland but the boundaries with this organ are sharp. A striking.feature of the tumor is presence of a focally prominent myxoid stroma, which in some areas forms cyst-like structures devoid of a lining and sometimes containing a central blood vessel, somewhat reminiscent of those seen in thymomas and some types of sweat gland tumors. A few of the cystic spaces (not shown in the photos distributed to the participants) are lined by squamous epithelium. There is no amyloid. Immunohistochemically, the tumor cells are positive for vimentin and keratin, and negative for thyroglobulin, chromogranin, calcitonin, S100 protein, and desmin. The features of this tumor correspond to the entity originally described as spindle epithelial tumor with thymus-like differentiation and known acronymically as SETTLE . [1] It is one of the four thymic or branchial arch-related tumors of the neck we described some years ago, the other three being ectopic hamartomatous thymoma (EHT), ectopic (cervical) thymoma, and ca rcinoma s howing t hymus- l ike elements (CASTLE). [1] Ectopic (cervical) thymoma is easy to understand and define: it is simply a tumor with the typical features of thymoma (usually of the AB type) that is located in the neck rather than in the mediastinum, presumably because of a failure of migration of the branchial arch-derived thymic Anlage . CASTLE is also easily understood. It is a thymic carcinoma of either keratinizing or non-keratinizing type that occurs ectopically in the neck rather than in the mediastinum. As a matter of fact, it could just.as easily be designated as an ectopic (cervical) thymic carcinoma. EHT and SETTLE belong to a different category because neither resembles any type of mediastinal thymoma. Rather, they seem to be characteristic of the cervical location. They share the feature of being predominantly or exclusively composed of spindle cells, thus simulating tumors of various types, particularly those of a mesenchymal nature. In both instances, an important clue to the diagnosis is the presence of foci of clearcut epithelial structures, sometimes merging with the predominant spindle cells. [1] Another curriosity, which surely must have a biologic explanation, is the fact that EHT is seen almost exclusively in males whereas ectopic thymoma develops almost always in females. [1] SETTLE, which is the subject of this presentation, is the most mysterious member of the group and the one must commonly misdiagnosed. Its differential diagnosis includes most of the spindle cell tumors of the region, including peripheral nerve sheath tumors; the spindle cell variants of thyroid medullary carcinoma, follicular adenoma and papillary carcinoma, germ cell tumors (because of the occasional presence of peculiar gland-like structures) and - most of all - synovial sarcoma. As a matter of fact, it is sometimes impossible to tell SETTLE apart from a synovial sarcoma on morphologic grounds, particularly in the cases of SETTLE with a monomorphic spindle cell appearance ("monophasic" type). [2] Some authors have even voiced the possibility of most or all cases diagnosed or reported as SETTLE being actually synovial sarcomas. A molecular study done by Folpe et al presented at the USCAP meeting last year showed instead that cases with the morphologic features of SETTLE lack the SYT-SSX gene fusion that characterizes synovial sarcoma. [4] SETTLE occurs most often in adolescents, but it has also been seen in infants and adults. [6] It shows no apparent sex predilection. Most cases are found within or adjacent to the thyroid gland (in striking contrast with EHT, which is almost always supraclavicular or suprasternal). The histology is usually bland, although cases with significant atypia and necrosis are on record. [5] It grows slowly, but has a tendency to develop late blood-borne metastases to places such as lung and kidney, sometimes as late as 22 years after the initial therapy. [3] It can also metastasize to regional lymph nodes. [7] Diagnosis Thyroid, thyroidectomy – Spindle epithelial tumor with thymus-like differentiation ("SETTLE") References Chan JKC, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol 1991;22:349-367 Chetty R, Goetsch S, Nayler S, Cooper K. Spindle epithelial tumor with thymus-like element (SETTLE): the predominantly monophasic variant. Histopathology 1998;33:71-74. Cheuk W, Jacobson AA, Chan JKC. Spindle epithelial tumor with thymus-like differentiation (SETTLE): a distinctive malignant thyroid neoplasm with significant metastatic potential. Mod Pathol 2000;13:1150-1155. Folpe AL, Loyd RV, Bacchi CE, Rosai J. Spindle epithelioid cell tumor with thymus-like elements (SETTLE): A morphologic, immunohistochemical and molecular geneticstudy of 13 putative cases Mod Pathol 2008; 21, Suppl 1, 235A. (Abstract). Kirby PA, Ellison WA, Thomas PA. Spindle epithelial tumor with thymus-like differentiation (SETTLE) of thyroid with prominent mitotic activity and focal necrosis. Am J Surg Pathol 1999;23:712-716. Satoh S, Toda S, Narikawa K, Watanabe K, Tsuda K, Kuratomi Y, Sugihara H, Inokuchi A. Spindle epithelial tumor with thymus-like differentiation (SETTLE). Youngest reported patient. Pathol Int 2006;56:563-567. Yu A, LiVolsi V. Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid with neck lymph node metastasis. A case report. Endocr Pathol 2005;16:139-144.