Serous Borderline Tumor Progressing to Low-Grade Serous Carcinoma after 35 Years: a Case of Extended Latency with Molecular Evidence of Clonal Relationship

Background:Low-grade serous ovarian carcinoma (LGSOC) is an uncommon epithelial malignancy that typically arises in the setting of a serous borderline ovarian tumor (SBOT), with the majority of low-grade serous neoplasms harboring mutually exclusive mutations in KRAS, BRAF, or NRAS. The time to progression from SBOT to LGSOC is highly variable with a median of 10 years, with the longest previously reported interval of 39 years. LGSOC often presents at advanced stage with a high propensity for recurrence despite surgical intervention (the primary treatment modality) and systemic pharmacologic treatments. Case Presentation:Herein, we present the case of a 62-year-old patient with a diagnosis of advanced LGSOC that presented 39 years after her initial diagnosis and 35 years after last documented surgical resection of SBOT. Additionally, we describe the utilization of molecular testing for a BRAF V600E mutation in both the SBOT and LGSOC specimens, suggesting a clonal relationship between the two neoplasms in this case, and also providing an indication for targeted therapy to which this patient demonstrated a rapid and robust response. Conclusion:This case exemplifies the long-term natural history of low-grade serous neoplasia and highlights how the incorporation of molecular studies can improve diagnostic certainty and guide therapy selection for patients. Further, we provide a review of the literature on SBOT progression to LGSOC, including risk factors for progression and therapeutic options to treat recurrent/progressive disease.