HPV-independent Squamous Cell Carcinoma With Choriocarcinomatous Differentiation in Uterine Cervix: Case Report With Molecular Characterization

This report pertains to a rare case of cervical squamous cell carcinoma (SCC) with choriocarcinomatous (CC) differentiation in a 77-yr-old woman. The patient developed lung and mediastinal metastases 3 mo after surgery and died at 5 mo. Histopathologically, the tumor shows a mixed pattern of SCC and CCs. Both SCC and CC components showed a mutant-type p53 immunostaining and no high-risk HPV mRNA signals by RNAscope. PD-L1 was positive in SCC and CC, with a combined positive score of 10 and 90, respectively. Short tandem repeat analysis indicated identical alleles among CC, SCC, and the normal tissues. Targeted next-generation sequencing demonstrated high tumor mutational burden (>10 mutations/Mb) and 2 common driver mutations [TP53 (c.853G>A) and TERT (c.-146C>T)]. This is the first report of an HPV-independent cervical SCC with choriocarcinomatous differentiation, supporting a clonal origin with divergent differentiation, and suggesting comprehensive therapies combining immunotherapy and pathway inhibitors for this aggressive cancer.