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Byline: Ichiro Fukai, Akira Masaoka, Takahiko Hashimoto, Yosuke Yamakawa, Hiroshi Niwa, Masanobu Kiriyama, Tadaaki Eimoto Abstract: There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to cytokeratins 7 and 13. Among keratinizing squamous cell carcinomas, all thymic carcinomas reacted with antibody specific for cytokeratin 7 (9/9, 100%), whereas no staining reaction was seen in lung carcinomas (0/5, 0%) (p < 0.01). This finding can be used as a diagnostic aid in primary thymic keratinizing squamous cell carcinomas to expedite treatment and prognosis. Cytokeratin 7 and cytokeratin 13 monoclonal antibodies reacted with almost all cases of thymic carcinoma. Applications of monoclonal antibodies specific for certain cytokeratins, especially 7 and 13, may be helpful in the diagnosis of other subtypes of thymic carcinomas. (J THORAC CARDIOVASC SURG 1995;110:1670-5) Author Affiliation: Nagoya, Japan Article History: Received 18 November 1994; Accepted 3 March 1995 Article Note: (footnote) [star] From the Second Department of Surgery a and the Second Department of Pathology, b Nagoya City University Medical School, Nagoya, Japan., [star][star] Dr. Masaoka is organizer of the project 'Function of Thymoma,' which is supported by a grant from the Ministry of Health and Welfare of Japan., a Address for reprints: Ichiro Fukai, MD, Second Department of Surgery, Nagoya City University Medical School, Mizuho-ku, Nagoya, Japan., aa 0022-5223/95 $5.00 + 0, acents 12/1/64937

Background. Thymus consists of some distinct epithelial cells that contain different sets of cytokeratins (CK). Epithelium-derived tumors maintain the expression of some of the CK of the specific nontransformed cells. Therefore, it seems reasonable to hypothesize that thymic epithelial tumors may differentiate toward distinct subsets of intrathymic epithelial cells in terms of CK expression. Methods. Eighty-one thymomas and 14 thymic carcinomas were studied immunohistologically using monoclonal antibodies specific for a single CK or a CK pair. Results. Thymic epithelial neoplasms could not be distinguished from each other on the basis of the profile of CK expression because the degree of overlap was extensive. However, polygonal cell thymomas differentiate toward a CK13-positive cortical subset that is rare in normal thymus. Spindle cell thymomas differentiate toward a CK13-positive medullary subset. Mixed cell thymomas are comprised of a CK13-positive medullary subset and a CK13-negative medullary subset, both of which are typical in normal thymus. CK18 was expressed to a greater extent on the epithelium of thymic carcinomas than on that of thymomas. Polygonal cell thymomas more frequently were invasive than spindle and mixed cell thymomas. Conclusions. There is a possibility that the epithelium of polygonal cell thymomas is immature because it is a phenotypically unusual subset in normal thymus. A thymic carcinoma arising in a thymoma has been reported, although the relationship between the thymoma and the thymic carcinoma was not clear. Nevertheless, given the similar cellular differentiation of thymoma and thymic carcinoma, CK18-positive epithelium in thymomas may be transformed into thymic carcinoma cells in certain conditions. Cancer 1993; 71:99-105.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation of gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditons. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms. Cancer 1992; 70:2077-2081.