Indian Pediatr 2012;49: 482-484
Recurrent Thyroid Nodule: Spindle Epithelial
Tumor with Thymus-like Differentiation (SETTLE)
Ashu Rastogi, Uma Nahar Saikia, Ashok Kumar Gupta* and Anil Bhansali
From the Departments of Endocrinology and
*Otolaryngology, PGIMER, Chandigarh, India.
Correspondence to: Dr Anil Bhansali, Professor and
Head, Department of Endocrinology, PGIMER,
Chandigarh 160 012, India.
Received: June 21, 2011;
Initial review: July 20, 2011;
Accepted: September 5, 2011.
Thyroid nodules are uncommon in childhood and recurrent thyroid nodules
even rarer. Spindle epithelial tumor with thymus-like differentiation
(SETTLE), a rare and distinctive low-grade neoplasm is amongst the
differential diagnosis of solitary thyroid nodule in children. We
describe a boy who underwent completion thyroidectomy for SETTLE in the
thyroid remnant four years after initial lobectomy was performed for the
same diagnosis. Patients with SETTLE are to be closely followed as
multifocality may manifest and be detected later.
Key words: Cytokeratin, Spindle epithelial tumor with
thymus-like differentiation (SETTLE), Thyroid.
Thyroid nodules are
uncommon in childhood particularly in iodine sufficient regions and
recurrent nodules are even rarer. The prevalence of palpable thyroid
nodules in childhood is about 1.5%. The differential diagnosis of
solitary thyroid nodule in children are colloid nodule/adenoma,
thyroid cyst, lymphocytic thyroiditis, differentiated thyroid
malignancy, medullary thyroid carcinoma and rarely spindle
epithelial tumor with thymus-like differentiation . Thyroid
nodules are more often malignant in childhood than in adulthood .
Spindle epithelial tumor with thymus-like
differentiation (SETTLE) is a rare and distinctive low-grade
neoplasm of children and adolescents which usually presents as
asymptomatic mass or nodule in the neck. Previously it has been
described as thyroid spindle cell tumor with mucinous cysts,
malignant teratoma and thymoma of the thyroid gland . SETTLE is a
tumor derived from ectopic thymus or branchial pouch remnants and
was formally characterized as SETTLE by Chan and Rosai .
Histopathology and immuno-histochemistry are the gold standard for
confirming the diagnosis. There have been less than 30 reported
cases of SETTLE in the available literature, and none of a
multicentric/recurrent SETTLE [5,6]. We report a case of
multicentric SETTLE in either of the lobes of thyroid in a young
A 9-year-old boy presented with progressively
increasing swelling along right side of the neck for 6 months. He
had no history of hoarseness of voice, difficulty in deglutition or
breathing, cold intolerance, constipation or symptoms suggestive of
hyperthyroidism. He had no history of exposure to radiation and no
family history of autoimmune thyroid disease or thyroid malignancy.
Ultrasonography detected a hypoechoic mass in right lobe of thyroid
and aspiration cytology suggested SETTLE. He was subjected to
lobectomy and histopathology confirmed the diagnosis of SETTLE.
During follow up, at the age of 13 years he was
detected to have nodular swelling in left lower part of the neck.
General and systemic examination was essentially normal except for a
scar mark of previous surgery above the suprasternal notch in the
midline. Tanners sexual maturity staging was G2, P2. He had a 3×2
cm firm swelling in the left lobe of thyroid, moving with
deglutition, however right lobe could not be palpated. On
investigations, his hematological parameters were within normal
limits. Biochemical investigations revealed albumin adjusted calcium
9.1 mg/dL, phosphate 4.3 mg/dL, alkaline phosphatase 188 IU/mL.
Hormonal investigations revealed T4 7.8 µg/dL, T3 1.7 ng/dL (0.8-1.8
ng/dL), TSH 1.91 µIU/mL (0.5-4.5 µIU/mL), anti thyroid peroxidase 15
IU/mL (<35IU/mL) and calcitonin 5.7pg/mL (<18.2 pg/mL).
Ultrasonography showed 3×2 cm hypoechoic,
homogenous lesion in the left lobe of the thyroid. CT scan confirmed
the same mass, with extensions into tracheo-esophageal groove and
loss of fat planes with esophagus posteriorly, without any evidence
of calcification or necrosis. Suspecting a malignant tumor of
thyroid PET-CT was done which revealed mild FDG uptake in ill-
defined nodule in left lobe of thyroid.
Fine needle aspiration cytology (FNAC) showed
cellular smears composed of spindle shaped cells with oval,
elongated nucleus suggestive of spindle cell tumor of thyroid. The
patient underwent total thyroidectomy. The thyroid specimen weighed
13 g, containing left lobe of thyroid with mass in left upper pole.
On cut surface a relatively circumscribed tumor was identified.
Micro-scopically, the tumor cells were arranged in form of vague
nodules separated by fibrous septa. Tumor cells were arranged in
short interlacing fascicles with oval to spindle shaped and
elongated vesicular nuclei. A mitotic count of 6-7/10 high power
fields was observed. Immunohistochemistry showed diffuse positivity
for cytokeratin, vimentin and smooth muscle actin. Calcitonin and
CD68 staining were negative ruling out medullary carcinoma and
histiocytic lesions of thyroid and overall features suggesting a
diagnosis of SETTLE. The patient received replacement doses of
levothyroxine after total thyroidectomy and is disease free for last
Spindle epithelial tumor with thymus-like
elements is an extremely rare tumor of the thyroid, characterized by
the proliferation of spindle cells with both epithelial and stromal
characteristics. The most common presentation of SETTLE is a nodular
thyroid swelling in childhood or adolescence .
The age at presentation of patients with
SETTLE range from 4 to 59 years, but the tumor occurs predominantly
in children, adolescents, and young adults . Clinically, the
neoplasm usually manifests as a firm mass involving one lobe of the
thyroid for a variable duration. Less commonly, the entire gland is
enlarged with hard consistency, and without palpable nodules,
mimicking thyroiditis . The present case also presented with
unilateral hard swelling. Clinically, the possibilities of nodular
goiter, differentiated thyroid malignancy, medullary carcinoma of
thyroid and spindle cell tumors of thyroid were considered.
Ultrasound of the neck usually shows a clearly
demarcated, solid nodule, except for a few cases in which no
nodularity is found and a diffusely hypoechoic structure typical for
autoimmune thyroditis is detected . Tumors appear cold
scintigraphically and display heterogeneous solid and cystic
densities on CT scan. Due to absence of specific clinical symptoms,
radiologic findings, or serum markers, a diagnosis of SETTLE is
almost always made after histopathologic evaluation as also in the
Certain histological features, including
incomplete lobulation, perivascular spaces, biphasic epithelioid/epithelial
and spindle cell populations, cysts and cleft-like spaces, and rare,
thin epithelial ribbons suggest thymic differentiation. In addition
to morphology, immunohistochemistry is important for making the
diagnosis of SETTLE. The tumor is typically positive for cytokeratin,
vimentin, S-100, smooth muscle actin, and muscle-specific actin and
negative staining for EMA, CEA,CK19, calcitonin, thyroglobulin and
chromoganin A [6,10]. We also observed positivity for these primary
antibodies, hence confirming the diagnosis of SETTLE.
Although SETTLE is considered a tumor with low
grade malignant potential, aggressive behavior has been reported in
some cases . The neoplasm grows slowly and may cause lymph node
and pulmonary metastases many years after diagnosis. Erickson noted
that 35% of all reported cases of SETTLE had one metastasis during
their course, whereas Cheuk noted a significant metastatic rate of
71% [7,10]. Metastatic disease has also been described up to 22 and
25 years after the initial operative intervention. Despite the
occurrence of metastasis, long-term survival is observed after
thyroidectomy. The index patient had a recurrence in other lobe of
the thyroid after 4 years of initial presentation and now is disease
free for last 2 years.
Formal treatment algorithms have not been
established for SETTLE because of the rarity of this tumor; partial
thyroidectomy is the current standard of care. However the index
case underwent completion thyroidectomy for SETTLE in the thyroid
remnant four years after initial lobectomy performed for the same
diagnosis. Patients with SETTLE are to be closely followed as
multifocality may manifest and be detected later.
Contributors: AR involved in patient care and
writing the manuscript. UNS reviewed histopathology. AKG performed
the surgery. AB involved in patient care and editing the manuscript.
Funding: None; Competing interests:
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