To the editor:

We appreciate the opportunity to respond to preprint copies of correspondence from Lensch and Ince and the response from Atala and Furth.

From our point of view, most of the problems and controversies mentioned in this correspondence have arisen from the inconsistent usage of the terms teratoma and teratocarcinoma by many scientists working in this field. Thus, we encourage the editors of Nature Biotechnology to standardize the terminology, at least for human embryonic stem (ES) cell–derived xenografts.

In our view, the term teratocarcinoma should be used only for malignant tumors, which in this context are malignant by virtue of the continued presence of stem cells—the embryonal carcinoma (EC) cells1. EC cells, as suggested by almost all studies on mouse- and human-derived cells, are the malignant equivalents or cognates of ES cells2. Any pathologist trained to identify human EC cells should be able to distinguish malignant teratocarcinomas from benign teratomas, which are defined as tumors composed only of somatic tissues and devoid of EC cells. In an experimental setting, the malignancy of a tumor due to the presence of morphologically identifiable EC cells can be tested by re-transplantation to a new host.

The distinction between teratomas and teratocarcinomas is crucial, especially for the future usage of ES cells in human medicine. Using xenografting as an essential preclinical safety control, one could predict that the ES cell lines that form only teratomas are 'benign' or 'safe' for human usage, whereas the cell lines that produce teratocarcinomas are 'malignant' and not safe for injection into humans3. Thus, we would discourage the indiscriminate usage of terms 'teratoma' and 'teratocarcinoma', even though in the past some eminent scientists have used those term interchangeably and even as synonyms. Previous imprecision is, in our opinion, not a valid justification for future use of a confusing terminology.

A minor but not insurmountable problem pertains to the usage of 'teratocarcinoma' for tumors produced from human ES cells. Even though the term 'teratocarcinoma' has been used as a synonym for malignant teratoma in mice for more than four decades, most leaders in human pathology have consistently refused to accept it. In the recent consensus book on human testicular tumors compiled by the experts of the World Health Organization (WHO; Geneva, Switzerland)4, the term teratocarcinoma is mentioned only in passing for the animal model of human germ cell tumors. Because the work on human ES cells is, in a sense, a continuation of the experiments first performed on mouse ES cells and teratocarcinoma-derived EC cells, we feel that the term 'teratocarcinoma' will be more readily accepted by laboratory researchers than diagnostic pathologists. At least it is less cumbersome than the WHO-recommended term “mixed embryonal carcinoma and teratoma” or indeed the British classification “malignant teratoma intermediate4”.