Somatic carcinomas with yolk sac tumor differentiation in the female genital tract: clinicopathological and molecular analysis of four cases with a literature review

Somatic carcinomas with yolk sac tumor (YST) differentiation in the female genital tract are exceedingly rare and diagnostically challenging. This study aimed to characterize their clinicopathologic, immunohistochemistry (IHC) and molecular features and to explore potential therapeutic implications. Four cases of somatic carcinoma with YST differentiation diagnosed at Peking University People's Hospital between 2019 and 2025 were retrospectively analyzed. Clinical data, pathological features, and IHC were analyzed. Next-generation sequencing (NGS) was performed in two cases. In addition, the findings were also compared with those of the three largest recent series reported in the literature. The four patients were aged 44-69 years. Primary sites included the cervix, endometrium, and ovary. Two cases showed significantly elevated AFP levels. Histologically, all tumors showed biphasic differentiation with coexisting somatic carcinoma and YST components. The YST component exhibited reticular/microcystic, papillary, solid, and hepatoid-like patterns, whereas Schiller-Duval bodies were absent. Immunohistochemically, the YST component showed diffuse SALL4 and Glypican-3 expression, focal to diffuse AFP positivity. All tumors showed aberrant p53 expression. NGS identified TP53 mutations, together with RICTOR amplification in one case. Two patients with FIGO stage III-IV disease died within 7 months after surgery, whereas the two patients with FIGO stage I-II disease remained disease free. These tumors are rare but aggressive somatically derived neoplasms. Accurate diagnosis requires integration of morphology and IHC. This study expands the clinicopathologic and molecular spectrum by documenting a case arising in cervical gastric-type adenocarcinoma and identifying RICTOR amplification in this setting.