Signs o’ the Times. The Quiet Revolution of Molecular Pathology in Gynecologic Oncology: A Narrative Review

Objective: To provide an updated overview of how molecular pathology is reshaping diagnostic, prognostic, and therapeutic paradigms in gynecologic oncology and redefining the role of the gynecologic pathologist in the era of precision medicine. Mechanism: Advances in next-generation sequencing (NGS) and large-scale genomic initiatives have enabled comprehensive molecular characterization of endometrial, ovarian, and cervical carcinomas. The integration of genomic, immunophenotypic, and clinicopathologic data supports a multidimensional diagnostic framework that refines risk stratification and guides targeted and immune-based therapies. Emerging tools, including liquid biopsy, digital pathology, and artificial intelligence (AI), are further advancing the clinical integration of molecular data. Findings in Brief: In endometrial carcinoma (EC), molecular classification complements and often surpasses morphology-based systems by providing more accurate prognostic assessment and informing therapeutic decision-making. In ovarian carcinoma, assessment of breast cancer susceptibility gene (BRCA) alterations and homologous recombination deficiency (HRD) has become central to personalized treatment strategies. In cervical carcinoma, although persistent high-risk human papillomavirus (HPV) infection remains the principal oncogenic driver, additional genomic alterations are increasingly being incorporated into the management of advanced disease. Furthermore, NGS enables the identification of germline alterations associated with hereditary cancer syndromes, thereby reinforcing the pathologist’s role in identifying familial cancer predisposition and supporting appropriate referral for genetic counseling. Conclusions: Molecular pathology is driving the transition toward an integrated, biology-driven model of gynecologic oncology, positioning the gynecologic pathologist as a key clinical integrator in precision medicine.