On the development of metastasizing tumors of the rat thyroid gland after combined administration of nitrosomethylurea and methylthiouracil.

Seventy-five female Wistar rats of 150 g each were given 3 X 40 mg/kg body weight nitrosomethylurea (NMU) and 4 weeks later until death (in the 9th-60th week) methylthiouracil (MTU), as a 0.1% solution in their drinking water. After 2 months, in the almost colloid-less thyroid gland individual foci appeared which consisted of sometimes colloid containing follicles with increased cytoplasmic and nuclear basophilia; they increased in number during the subsequent weeks and finally resulted in nodes with different morphologic structures. From the 16th week on there were tumors infiltrating the capsule, and after the 24th week there were angioinvasive carcinomas. Thirteen rats had developed lung metastasization after the 30th week. Cytology could only distinguish between the follicular carcinomas of low differentiation and the follicular adenomas. If these findings are applied to human pathology, one would have to reckon with adenomas which can develop their malignant characteristics without necessarily changing their histologic and cytologic appearance.