*3.5. Trophoblastic Cells*

Trophoblastic differentiation is a rare event in UC that has been recently reviewed by Przybycin et al. in a series of 16 cases [57]. The spectrum includes isolated syncytiotrophoblast cells interspersed in a conventional UC, mixed choriocarcinoma and UC, and pure choriocarcinoma. Same as in the yolk sac differentiation, trophoblastic changes are examples of somatically derived differentiations in non-gonadal tumors.

Syncytiotrophoblasts are detected as isolated multinucleated giant cells immersed in high-grade UC (Figure 2c). Choriocarcinoma differentiation appears as hemorrhagic areas at low-power magnification. A closer view of these areas reveals the typical mixture of trophoblastic and syncytiotrophoblastic cells immersed in a necro-hemorrhagic background (Figure 2d).

By immunohistochemistry, β-hCG is expressed in trophoblastic and syncytiotrophoblastic cells, as well as in the malignant urothelial cells in a significant number of cases. Interestingly, increased levels of seric β-hCG in patients with UC is an independent prognostic factor [58]. GATA3 positivity has been detected in more than 70% of trophoblastic tumors in a large series [59] and appears as a useful marker to be included in the diagnostic panel. SALL4 is focally positive in less than 50% of the cases [57] and is negative in the larger syncytiotrophoblastic cells [60]. HSD3B1, a novel marker specific to trophoblastic differentiation [61], has been detected in 100% of the cases [57].
