Transformation of an AFP-positive yolk sac carcinoma into an AFP-negative neoplasm. Evidence for in vivo cloning of the human parietal yolk sac carcinoma.

An alpha-fetoprotein (AFP)-positive ovarian yolk sac carcinoma of typical histologic appearance was surgically removed from a 19-year-old woman. The AFP-positive tumor recurred and was treated with x-rays and cytotoxic drugs to full remission, i.e., until no clinical or biochemical signs of tumor were evident. The second recurrence, which proved to be fatal, was noticed approximately 1 year after the initial diagnosis, but was not associated with elevated levels of serum AFP. At autopsy, the widespread tumor had the histologic appearance reminiscent of murine parietal yolk sac (PYS) carcinoma. The tumor cells did not form the characteristic histologic features of the classical human yolk sac carcinoma, did not secrete AFP, and were surrounded by extensive hyalinous extracellular matrix rich in laminin and collagen. It is thus shown that recurrent human yolk sac carcinomas could change their histologic morphology due to selective outgrowth and cloning of the parietal yolk sac component. Clinical recognition of this cloning is important because the PYS carcinoma cells do not secrete AFP, and the tumor growth cannot be biochemically monitored with this classical tumor marker.