Thyroid, Thyroidectomy – Spindle Epithelial Tumor with Thymus-Like Differentiation ("SETTLE")
Centro Diagnostico Italiano
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.
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
and known acronymically as SETTLE .  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
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
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
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. 
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).  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. 
SETTLE occurs most often in adolescents, but it has also been seen in infants and adults. 
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.  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.  It can
also metastasize to regional lymph nodes. 
Thyroid, thyroidectomy – Spindle epithelial tumor with thymus-like differentiation ("SETTLE")
- 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.