Case 2 -
Carcinoma Showing Thymus-like Differentiation (CASTLE) of the Thyroid
Syed Z. Ali, Johns Hopkins Medical Institutions, Baltimore, MD
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A 68 year-old man presented with sore throat and a lump in his right neck. Radiological imaging showed an irregularly enlarged right thyroid lobe. Ultrasound examination confirmed a 5.8 cm right mid pole thyroid nodule and multiple small lymph nodes in the neck, the largest one measuring 2.2 cm. A whole body CT did not reveal any other abnormalities. No significant past or family history was noted. An ultrasound-guided FNA of the right thyroid nodule was performed using 25-gauge needle. Direct smears were prepared and stained with Diff Quik and Papanicolaou stains.
Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant neoplasm located in the
thyroid and adjacent soft tissues which histologically resembles thymic carcinoma. Three cases of an
intrathyroidal tumor resembling a primary squamous cell carcinoma of the thyroid gland with a more
favorable prognosis were first reported in 1985 by Miyauchi et al. and designated as 'intrathyroidal
epithelial thymoma.' Several years later, Chan and Rosai described a number of rare tumors found in the
soft tissues of the neck and thyroid gland which were noted to be histologically similar to both
lymphoepithelioma and squamous cell type thymic carcinomas and designated these neoplasms as CASTLE.
Neoplasms of this entity have been postulated to originate from either ectopic thymus or remnants of
branchial pouches that retain the ability to differentiate along the thymic line. CASTLE occurs most
often in the fifth decade of life with a slight female predominance and is most commonly located in the
lower two thirds of the thyroid gland. The ability to distinguish CASTLE from either squamous cell or
anaplastic carcinomas of the thyroid gland is clinically important due to the fact that the latter two
entities are known to behave more aggressively and carry a worse prognosis.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Cytologically, the neoplasm appears as irregular sheets of poorly-differentiated (high-grade)
carcinoma cells entwined with small lymphocytes, such as in lymphoepithelioma occurring elsewhere. The
neoplastic cells contain round-to-oval nuclei, prominent eosinophilic nucleoli, low mitotic rate, sparse
amphophilic cytoplasm and ill-defined cell borders, with the most characteristic feature of small
reactive lymphocytes admixed with the neoplastic cells. The histopathology of CASTLE is characterized by
well-defined lobulated architecture, expansive growth pattern, poorly-differentiated malignant cells in
sheets intermixed with small lymphocytes, fibrous bands separating tumor lobules, whorl formations
similar to Hassall's corpuscles and increased pleomorphism of nuclei when compared to the conventional
thymoma. Differentiating thymic from thyroid origin is supported by immunoreactivity for markers
associated with thymic carcinoma such as CD5, bcl-2 and mcl-1 and negativity for TTF-1.
Anaplastic thyroid carcinoma. Metastasis to the thyroid.
Carcinoma Showing Thymus-like Differentiation (CASTLE) of the Thyroid.
Immunohistochemistry for CD5 is positive in the majority of CASTLE tumors with sensitivity and
specificity for CD5 in the diagnosis of CASTLE as 82% and 100% respectively. Other markers of thymic
origin that may provide utility in differentiating CASTLE from other thyroid neoplasms include HMWCK,
CEA, pC63, bcl-2, mcl-1 and negativity for TTF-1. The distinction between primary undifferentiated or
squamous cell thyroid carcinoma and a metastatic carcinoma from an unknown primary versus CASTLE is
important based on the knowledge that CASTLE is an indolently behaving tumor while the former two
entities confer a far worse prognosis. Due to the rarity of this tumor, exclusion of an undiagnosed
primary is necessary before rendering a diagnosis of CASTLE.
It is not possible to definitively diagnose CASTLE cytologically on fine needle aspiration (FNA) and
requires histological examination in addition to immunohistochemical studies.
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