Background: CASTLE (carcinoma showing thymus-like differentiation) is a rare tumor (accounting for less than 0.15% of thyroid neoplasms) with most of the reported cases from Asia. Although this tumor is rare, distinguishing it from more aggressive neoplasms is critical because of its improved prognosis. To date, there have been limited studies on its cytomorphological features. Herein, we review the cytomorphological features of 10 fine-needle aspiration (FNA) cases of histologically confirmed CASTLE and discuss the findings in light of the current literature. Methods: We retrospectively (1989-2016) identified 10 cases of CASTLE from 17,415 surgical cases of thyroid carcinoma from The Johns Hopkins Hospital and Fudan University Shanghai Cancer Center. The cases were reviewed for discrete cytomorphological characteristics. Results: All of the cases displayed predominantly single (dishesive) epithelial cell populations, high nuclear/cytoplasmic ratios, hyperchromatic to open/vesicular nuclei and macronucleoli. The majority of cases additionally showed hypercellular, three-dimensional fragments in a background of lymphocytes. The fragments displayed syncytial architecture without molding and rarely squamous differentiation. All cases lacked follicular differentiation, intranuclear inclusions, nuclear molding, or neuroendocrine-type chromatin. Conclusions: Cytopathological features alone do not appear to be distinctive or definitive of CASTLE but rather allow for the inclusion of CASTLE within the differential diagnosis. Procurement of cell block material is important and resulted in the single case of CASTLE accurately diagnosed on FNA. Cytopathological features that favored CASTLE included syncytial fragments of malignant cells with pleomorphic large nuclei, vesicular chromatin, and prominent nucleoli in a background of lymphocytes. These cytopathological findings in the appropriate clinicoradiological context warrant its inclusion in the reported differential diagnosis in order to be able to implement appropriate clinical management.

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