THYMIC EPITHELIAL TUMOR PROGRESSION IN AN SV40T TRANSGENIC MOUSE MODEL - CORTICAL THYMOMA-THYMIC CARCINOMA SEQUENCE

There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We e stablished a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma wit hin a predictable time span. Using this animal model and a morphologic al approach, thymic epithelial tumour progression was studied with ref erence to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the enti re spectrum from cortical type thymoma to thymic carcinoma. Thymic siz e tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiat ed thymic carcinoma. When SV40T TG mice (248 line) reached a certain a ge, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma-carcinoma sequence. When the mice were 9 weeks of age , the thymuses formed gross masses compatible with cortical thymoma. A t 14 weeks of age, WDTC appeared against the background of cortical th ymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullar y thymomas did not develop in the mice, and no transition from medulla ry-type thymomas to thymic carcinomas was observed. In this SV40T tran sgenic mouse model, thymic carcinoma is clearly preceded by cortical t ype thymoma. These transgenic mice may provide an interesting model fo r the progression from cortical thymoma to WDTC and/or high-grade carc inoma.