Nature Biotechnology responds:

A survey of the literature indicates no consensus on how to distinguish the terms 'teratoma' and 'teratocarcinoma'. The term 'teratocarcinoma' is used as a synonym for human tumors clinically known as “teratoma with embryonal carcinoma” (according to the World Health Organization) or “teratoma intermediate” (according to the British classification of germ cell tumors). Some pathologists include these tumors in the group of testicular 'nonseminomas' (also known as 'nonseminomatous germ cell tumors (NSGCT)') or use imprecise terms, such as 'malignant teratoma'. The somatic tissues in teratocarcinoma may be fully differentiated (equivalent to adult tissue) or only partially differentiated (corresponding to immature tissues in fetal organs).

On the basis of the above exchange and after expert consultation, Nature Biotechnology will adopt the term 'teratocarcinoma' to describe malignant tumors comprising both somatic tissues and undifferentiated malignant stem cells, identifiable as EC cells. EC cells are malignant equivalents of ES cells. Human EC cells should be identifiable microscopically according to the pathologic and immunohistochemical criteria used to identify human EC cells in malignant germ cell tumors of the ovary or testis or extragonadal sites. In an experimental setting, the malignancy of a tumor due to the presence of morphologically identifiable undifferentiated EC cells may be defined by their ability to form a new tumor after transplantation to a new host.

We will apply the term 'teratoma' only to tumors composed of normal, 'benign' somatic tissue and their immature (fetal) precursors derived from more than one of the three embryonic germ layers (ectoderm, mesoderm and endoderm). Teratomas comprising nonproliferating somatic tissue may be further labeled as 'benign', 'mature' or 'fully differentiated'. Teratomas composed of immature, proliferating fetal-like tissues may be labeled 'immature'.

It should be noted that almost all tumors produced in immunosuppressed mice from xenografted human ES cells have proven to be teratomas. Some data suggest that teratocarcinomas may occasionally be produced from human ES cells upon xenografting, but these tumors have not been fully documented.