Embryologic clues to human yolk sac tumors: a review

Morphological similarities and differences in the developmental structure of the human yolk sac and human yolk sac tumors (HYSTs) are reviewed to determine the histogenesis of the currently recognized multiple tumoral patterns. Although many equivalent histochemical markers, secretory hyaline globules, and hemopoiesis occur in both HYSTs and the secondary human yolk sac (SHYS), few similarities are found in their comparative morphology. For example, HYSTs do not reproduce the characteristic morphology of SHYS with its large, clear cells and endodermal and intracellular tubules; basement membrane is abundant in tumors but only an inapparent and temporary structure in the SHYS; no Schiller-Duval sinuses are found in either primary or secondary human yolk sacs, and the plentiful mesenchymal (mesoblastic) components of tumors are absent in the SHYS except for the collagenous connective tissue that occurs during regression. Unlike the SHYS, which is a terminal structure incapable of polydifferentiation and only rarely develops any somatic structures, HYSTs frequently differentiate tissues of endodermal origin such as intestine, liver, and even lung. The primary human yolk sac is capable of multiple differentiation, both endodermal and possibly mesenchymal, as well as its ultimate differentiation into the SHYS with its characteristic endodermal markers. Thus, it seems more appropriate to correlate the comparative morphology of HYSTs with the primary human yolk sac, rather than the SHYS, and, in the light of this, reconsider their classification as extraembryonally differentiated tumors.