Chien-Chin Chen1,2(陳建欽), Yi-Jun Jian1 The Liquid-based Cytology of a Carcinoma Showing Thymus-like Differentiation in the thyroid (CASTLE) Chien-Chin Chen1,2(陳建欽), Yi-Jun Jian1 1Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan. 2Department of Cosmetic science, Chia Nan University of Pharmacy and Science, Taiwan. Case Presentation A 38 year-old lady complained of persistent hoarseness for 3 months with intermittent chocking. The laryngoscope showed incomplete glottic closure with right vocal paralysis. The neck ultrasonography revealed a right thyroid mass. The liquid-based cytology from fine needle aspiration was interpreted as suspicious of malignant neoplasm without further definitive classification. Computerized tomography (CT scan) revealed a right thyroid tumor with compression to trachea. With intraoperative consultation, she received radical thyroidectomy and central neck lymph node dissection. Grossly, in the right thyroid, there was an ill-defined gray white infiltrating tumor, measuring 2.7 x 2.5 x 1.6cm. Microscopically, the tumor consisted of lobules of solid sheets of epithelial cells with focal whorls resembling Hassall's corpuscles, variable lymphocytes infiltrate, and separated by fibrous bands. Tumor cells had indistinct cell borders, ill-defined cytoplasm with eosinophilic or amphophilic cytoplasm, round to oval vesicular nuclei, and prominent nucleoli. Immunohistochemically, tumor cells were positive for pan-cytokeratin, p63, p40, CD5, and CK5, but negative for thyroglobulin, TTF-1, CD56, TdT, EBER. Extensive extrathyroid tumor invasion into muscles and perithyroid soft tissues were also present with one metastatic lymph node. She received postoperative radiotherapy for tumor involvement in resection margins, and got no evidence of tumor recurrence for 7 months. A B C D E F E Figure 2: (A:X100,B-E:X400, BD SurePath™) The liquid-based cytology was hypercellular with cohesive three dimensional sheets of atypical cells which revealed high nuclear: cytoplasmic ratios, round to ovoid nuclei, irregular nuclear contours, and distinct nucleoli with moderate degree of lymphocytes infiltrate in the background. The nuclear chromatin was coarsely granular. Focal squamoid keratinization is found. (F: Liu stain X400) The intraoperative touching cytology revealed solid sheets of tumor cells. Figures & Clinical Images A B A B C C CD5 Figure 1: (A) Incomplete glottic closure with right vocal paralysis by laryngoscope; (B) Neck ultrasonography showed a solid hypoechoic mass, 3.44cm, without calcification in right thyroid gland. (C) Computerized tomography with contrast revealed a right thyroid tumor with compression to trachea. Figure 3: (A) The tumor was composed of lobular architecture and fibrous bands separating. (HE, X40)(B,C)Solid nests of squamoid or epithelioid cells with whorls resembling Hassall’s corpuscles and variable lymphocytes infiltrate. (HE, B:X100, C:X200) CD5 staining is strongly positive in tumor cells. Only 42 cases of CASTLE in English literature were diagnosed with FNA. Our case is the only one providing liquid-based cytomorphology. The cytologic differential diagnoses might include insular carcinoma, anaplastic carcinoma, squamous cell carcinoma, metastatic lymphoepithelioma-like carcinoma, and follicular dendritic cell sarcoma. Most CASTLE cases could be screened out via FNA by nuclear atypia, but definite diagnoses were not rendered. Discussions Table 1. Diagnosis of CASTLE on the FNA biopsy Reference No. of cases Diagnosis of FNA biopsy Our case 1 Suspicious of malignant neoplasm Chang S, et al. 2012 1 High-grade malignant thyroid neoplasm Youens et al. 2011 1 Malignant thyroid neoplasm Hirokawa et al. 2010 7 Malignant tumor 1 Indeterminate (necrotic mass) Kim et al. 2008 1 Poorly differentiated carcinoma Yamazaki et al. 2008 1 Suggesting malignant tumor Cappelli et al. 2008 1 Malignant cells Chan et al. 2008 1 Papillary carcinoma Ito et al. 2007 1 CASTLE 19 Suspicious of thyroid Carcinoma of an unusual type Kusada et al. 2005 1 Malignant epithelial tumor Luo et al. 2005 1 Negative (red blood cells, fibrins , lymphocytes, and neutrophils) Kim et al. 2004 1 Malignant tumor Nassar et al. 2003 1 Hürthle cell neoplasm Gu et al. 1999 1 Poorly differentiated carcinoma Ahuja et al. 1998 1 Spindle-cell tumor Ng et al. 1996 1 Poorly differentiated carcinoma CASTLE, carcinoma showing thymus-like differentiation; FNA, fine-needle aspiration. Summary CASTLE is rare and, among the reported cases, the discussion on its cytologic findings, especially liquid-based cytology, is extremely limited. We presented a typical case for the cytomorphological correlation between cytology and histology.