Immunohistochemical staining for bcl-2 and mcl-1 in intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) and cervical thymic carcinoma.

Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE), a rare thyroid neoplasm, was recently shown to be immunoreactive for CD5, providing immunophenotypic evidence of previously postulated thymic differentiation. To assess whether ectopic malignant neoplasms with thymic differentiation display other markers associated with thymic carcinoma, we studied five cases of ITET/CASTLE, two cases of cervical thymic carcinoma, and one case of cervical thymoma for bcl-2 and mcl-1 immunoreactivity. Both of these antiapoptosis proto-oncogenes have been reported to be expressed by the majority of true thymic carcinomas but only a minority of thymomas. All of the five cases of ITET/CASTLE, both CD5-positive cervical thymic carcinomas, and one CD5-negative cervical thymoma were immunoreactive for bcl-2, as were 10 (91%) of 11 thymic carcinomas arising in the thymus, in contrast to 6 (25%) of 24 benign and invasive thymomas arising in the thymus. Similarly, all of the five cases of ITET/CASTLE, both cervical thymic carcinomas, but not the cervical thymoma, were immunoreactive for mcl-1, as were 9 (90%) of 10 thymic carcinomas, in contrast to 6 (33%) of 18 benign and invasive thymomas. We conclude that dual immunoreactivity for bcl-2 and mcl-1 is a feature of malignant neoplasms with thymic differentiation in general, both within the thymus and at ectopic sites.