Yolk sac tumours revisited. A review of their many faces and names

We review the current knowledge on human yolk sac tumours (YSTs) 50 years after their initial description. Their complex nomenclature and histogenesis stress the fact that they are not a discrete entity, but represent a multifaceted group of neoplasms, for which the term primitive endodermal tumours would be more appropriate, accounting for their capacity to differentiate into various extraembryonal and somatic cell types. Different histological patterns of human YSTs correlate with the developmental potential of primitive endoderm and mesenchyme, but they are also similar to some murine experimental tumours. Exceptionally, YSTs replicate the tubular structures of the human yolk sac and allantois. Endodermal somatic differentiation reproduces pulmonary, intestinal and hepatic tissues and are identical with some, embryonal-type endodermal, gastric and lung carcinomas, which are indistinguishable from YSTs. YSTs may show an overgrowth of their mesenchymal (sarcomatous) and epithelial components (such as mucinous carcinoma or carcinoid) and also be a source of haematological malignancies. YSTs associated with non-germ cell tumours probably originate from malignant pluripotent somatic stem cells. Only AFP and glypican-3 are characteristic immunohistochemical markers. Pluripotent antibodies (SALL4, Lin28, IMP-3) help in differential diagnoses, while some differentiation markers (CDX2, TTF-1, HepPar1) facilitate recognition of unusual variants of YSTs.