Beyond organ-based therapy: Genome-directed treatment of metastatic gastric-type endocervical adenocarcinoma

Background Gastric-type endocervical adenocarcinoma (GEA) is a rare, HPV-independent subtype of cervical cancer associated with aggressive behavior and poor response to conventional treatment for cervical cancer. Optimal management is hindered by limited clinical trial data specific to this rare cancer subtype. Genomic analysis holds the promise of identifying better therapy and improving outcomes in this and other rare diseases. Case presentation An 81-year-old woman presented with vaginal discharge and postmenopausal bleeding and was diagnosed with HPV-independent GEA. Imaging demonstrated a locally advanced cervical mass and a concurrent pancreatic tail lesion, raising concern for either metastatic cervical cancer or a synchronous primary pancreatic adenocarcinoma. Comparative next-generation sequencing demonstrated identical pathogenic alterations in KRAS and TP53 , strongly supporting a shared clonal origin. Integration of the clinical, pathologic, and molecular findings favored metastatic GEA with a pancreatic-like phenotype, and pancreatic cancer-directed chemotherapy was initiated. The patient received gemcitabine and nab-paclitaxel and achieved a complete radiographic and metabolic response after six cycles. She subsequently underwent laparoscopic hysterectomy, with only microscopic residual disease at the cervicovaginal margin. Conclusions Comparative molecular profiling may help clarify the relationship between tumors at different anatomic sites and inform individualized treatment selection in diagnostically challenging cases of GEA. The observed response to pancreatic cancer-directed chemotherapy in this case is hypothesis-generating and requires further investigation.