Cellular and Molecular Biology



Intrathyroid epithelial thymoma (ITET) and carcinoma showing thymus-like differentiation (CASTLE). CD5-positive neoplasms mimicking squamous cell carcinoma of the thyroid

Kennichi Kakudo1,2, Yanhua Bai3, Takashi Ozaki2, Kei-ichi Homma4, Yasuhiro Ito5 and Akira Miyauchi5

1Department of Medical Technology, Kobe-Tokiwa University, Kobe, Japan, 2Department of Human Pathology, Wakayama Medical University, Kimiidera, Wakayama, Japan, 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, P.R. China, 4Division of Pathology, Niigata Cancer Center Hospital, Niigata, Japan and 5Department of Surgery, Kuma Hospital, Kobe, Japan.

Offprint requests to: Prof. K. Kakudo, MD, PhD, Department of Medical Technology, Kobe-Tokiwa University, Kobe-city, 653-0838 Japan. e-mail: k-kakudo@kobe-tokiwa.ac.jp

Summary. Carcinoma of possible thymic epithelial origin may occur within the thyroid gland, which was first reported by Miyauchi et al. as intrathyroid epithelial thymoma (ITET). ITET is a rare tumor comprising about 0.08% of all primary thyroid malignancies. It is a low-grade thyroid carcinoma with squamous cell differentiation whose overall survival rate was found to be 71%. Lymph node metastasis at surgery was found in 40% and hematogenous metastases developed in bones, liver and lungs. This tumor grows within the thyroid gland and invades into the thyroid parenchyma as well as into the extrathyroid structures. It is a well-circumscribed solid tumor with a sharp tumor border, but is not capsulated. After fixation, the cut surface of the tumor is gray-white in color and is a solid tumor with lobulation. Tumor calcification was not detected in our 15 cases. The tumor cells show solid sheets of growth with occasional keratinization without follicular or papillary structures. Lymphocytic infiltration in the stroma is one of the most characteristic features of this tumor. The tumor cells are polygonal epithelial cells with distinct nucleoli and ill-defined cell border. Positive immunoreactivity for CD5 is a key feature to differentiate it from undifferentiated carcinoma, poorly differentiated carcinoma, medullary (C cell) carcinoma and high-grade squamous cell carcinoma (so-called primary squamous cell carcinoma) of the thyroid. Negative immunoreactivity for calcitonin, TTF1 and thyroglobulin, and positive immunoreactivity for p63 and KIT are also helpful for differential diagnosis. Nuclear atypia is mild and mitoses are less frequent, with an intermediate proliferation index (MIB-1 labeling index is usually less than 20%), which are also helpful to differentiate it from high-grade primary squamous cell carcinoma of the thyroid. The tumors in our 15 cases demonstrate 3 histological subtypes: keratinizing squamous cell carcinoma type, non-keratinizing basaloid cell carcinoma (lymphoepithelioma-like) type and neuroendocrine carcinoma type, which correspond to subtypes of the mediastinal thymic carcinomas
. Histol Histopathol 28, 543-556 (2013)

Key words: Thyroid carcinoma, CD5, Squamous cell, Lymphoepithelioma, Neuroendocrine